Clinical trial NCT03492385
Conditions: Healthy
Sponsor: SFJ Pharmaceuticals, Inc.
Start date: 2018-04-03; Completion date: 2018-09-18
Enrollment: 64 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled, single ascending dose, sequential group study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PB2452 with and without ticagrelor pretreatment when administered to healthy male and female subjects.

Up to 6 dose levels will be evaluated. This study will have up to 10 cohorts and up to a total of approximately 76 subjects with either 4 or 8 healthy young subjects in Cohorts 1 through 9 or approximately 16 older subjects in Cohort 10. The starting dose of PB2452 will be 100 mg and the planned doses for subsequent cohorts are 300, 1000, 3000, 9000, and 18000 mg.

Detailed description:

Arms: arm 1: PB2452 Infusion or Placebo - Sodium Chloride arm 2: PB2452 Infusion or Placebo - Sodium Chloride arm 3: PB2452 Infusion or Placebo - Sodium Chloride arm 4: PB2452 Infusion or Placebo - Sodium Chloride With Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses arm 5: PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses arm 6: PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses arm 7: PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for a total of 5 doses arm 8: PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses arm 9: PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses and 180 mg 24 hours post-dose arm 10: PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg+90 mg BID for 5 doses
Interventions: intervention 1: PB2452 Infusion intervention 2: Placebo - Sodium Chloride intervention 3: Ticagrelor Oral Tablet - Pre-Treatment intervention 4: Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment
Intervention descriptions: intervention 1: 30 minute - 12 hour infusion intervention 2: 30 minute - 12 hour infusion intervention 3: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo intervention 4: Ticagrelor 180 mg + 90 mg BID for 5 doses prior to MEDI2452 (PB2452) or Placebo and Ticagerlor 180 mg 24 hours following MEDI2452 (PB2452) or Placebo

Protocol documents:
Prot_000.pdf: 
 
 
CLINICAL STUDY PROTOCOL 
 
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, SINGLE ASCENDING DOSE STUDY TO 
EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, 
AND PHARMACODYNAMICS OF MEDI2452 (PB2452) WITH AND 
WITHOUT TICAGRELOR PRETREATMENT IN HEALTHY 
VOLUNTEERS 
 
PROTOCOL NO. PB2452-PT-CL-0001 
Sponsor: 
PhaseBio Pharmaceuticals, Inc 
1 Great Valley Parkway, Suite 30 
Malvern, PA 19355 
Sponsor Contact: 
John Lee, MD, PhD 
CMO 
1 Great Valley Parkway, Suite 30 
Malvern, PA 19355 
 
Medical Monitor: 
Rahul Bhatnagar, MD 
Medical Monitor 
7551 Metro Center Drive, Suite 300 
Austin, TX 78744 
 
Version of Protocol: 
Final 1.0 
Date of Protocol:  
01 Feb 2018 
 
CONFIDENTIAL 
The concepts and information contained in this document or generated during the study are 
considered proprietary and may not be disclosed in whole or in part without the expressed, 
written consent of PhaseBio Pharmaceuticals, Inc. 
The study will be conducted according to the International Council for Harmonisation (ICH) 
harmonised tripartite guideline E6(R2): Good Clinical Practice. 
 






PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 4 
TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SIGNATURE PAGE ..................................................................................................................2 
INVESTIGATOR PROTOCOL AGREEMENT PAGE ........................................................3 
TABLE OF CONTENTS ...........................................................................................................4 
LIST OF TABLES ......................................................................................................................7 
LIST OF FIGURES ...................................................................................................................7 
PROTOCOL SYNOPSIS ..........................................................................................................8 
LIST OF ABBREVIATIONS ....................................................................................................20 
1. 
INTRODUCTION ..................................................................................................22 
1.1 
BACKGROUND INFORMATION .....................................................................22 
1.1.1 
Non-clinical Pharmacology ..............................................................................23 
1.1.2 
Benefit/Risk Assessment ..................................................................................24 
1.2 
RATIONALE FOR STUDY ................................................................................24 
1.3 
RATIONALE FOR DOSE SELECTION .............................................................25 
2. 
STUDY OBJECTIVES ...........................................................................................26 
2.1 
PRIMARY OBJECTIVES ....................................................................................26 
2.2 
SECONDARY OBJECTIVES .............................................................................26 
2.3 
EXPLORATORY OBJECTIVE ...........................................................................26 
3. 
INVESTIGATIONAL PLAN .................................................................................27 
3.1 
STUDY DESIGN .................................................................................................27 
3.2 
SELECTION OF STUDY POPULATION ..........................................................31 
3.2.1 
Inclusion Criteria ..............................................................................................31 
3.2.2 
Exclusion Criteria .............................................................................................32 
3.2.3 
Subject Restrictions During the Study..............................................................36 
3.3 
WITHDRAWAL OF SUBJECTS FROM THE STUDY .....................................37 
3.3.1 
Reasons for Withdrawal....................................................................................37 
3.3.2 
Handling of Withdrawals ..................................................................................37 
3.3.3 
Replacements ....................................................................................................38 
3.4 
STUDY TREATMENTS ......................................................................................38 
3.4.1 
Method of Assigning Subjects to Treatment Groups ........................................38 
3.4.2 
Treatments Administered ..................................................................................38 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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3.4.2.1 
Dose Escalation ............................................................................................40 
3.4.2.2 
Infusion or Allergic Reactions ......................................................................40 
3.4.2.3 
Dose-Limiting Toxicities ..............................................................................41 
3.4.2.4 
Stopping Criteria ...........................................................................................42 
3.4.3 
Identity of Investigational Product ...................................................................43 
3.4.4 
Management of Clinical Supplies.....................................................................43 
3.4.4.1 
Study Drug Packaging and Storage ..............................................................43 
3.4.4.2 
Study Drug Accountability ...........................................................................44 
3.4.5 
Blinding ............................................................................................................44 
3.4.6 
Breaking the Blind ............................................................................................45 
3.4.7 
Treatment Compliance ......................................................................................45 
3.4.8 
Prior and Concomitant Medications .................................................................46 
3.4.8.1 
Prior Medications and Therapies ..................................................................46 
3.4.8.2 
Concomitant Medications and Therapies .....................................................46 
3.5 
STUDY PROCEDURES ......................................................................................46 
3.5.1 
Pharmacokinetic Assessments ..........................................................................46 
3.5.1.1 
Pharmacokinetic Sample Collection .............................................................48 
3.5.1.2 
Bioanalytical Methods ..................................................................................49 
3.5.2 
Pharmacodynamic Assessments .......................................................................49 
3.5.2.1 
Pharmacodynamic Sample Collection ..........................................................50 
3.5.2.2 
Bioanalytical Methods ..................................................................................51 
3.5.3 
Safety Assessments ...........................................................................................51 
3.5.4 
Adverse Events .................................................................................................51 
3.5.4.1 
Adverse Event Definitions ............................................................................51 
3.5.4.2 
Eliciting and Documenting Adverse Events .................................................53 
3.5.4.3 
Reporting Adverse Events ............................................................................53 
3.5.4.4 
Assessment of Severity .................................................................................54 
3.5.4.5 
Assessment of Causality ...............................................................................55 
3.5.4.6 
Follow-up of Adverse Events .......................................................................55 
3.5.5 
Clinical Laboratory Testing ..............................................................................55 
3.5.6 
Vital Sign Measurements ..................................................................................57 
3.5.7 
Twelve-Lead Electrocardiogram ......................................................................57 
3.5.8 
Physical Examinations ......................................................................................58 
3.5.9 
Infusion Site Assessments ................................................................................58 
3.5.10 
Telemetry Monitoring .......................................................................................58 
3.5.11 
Immunogenicity ................................................................................................59 
3.6 
STATISTICAL ANALYSIS PLAN ......................................................................59 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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3.6.1 
Sample Size Calculations .................................................................................59 
3.6.2 
Analysis Populations ........................................................................................59 
3.6.3 
Statistical Analysis ............................................................................................59 
3.6.3.1 
Safety Analyses .............................................................................................60 
3.6.3.2 
Pharmacokinetic Analyses ............................................................................60 
3.6.3.3 
Pharmacodynamic Analyses .........................................................................61 
3.6.4 
Handling of Missing Data ................................................................................61 
3.6.5 
Interim Analyses ...............................................................................................61 
3.7 
DATA QUALITY ASSURANCE .........................................................................62 
4. 
INVESTIGATOR OBLIGATIONS ......................................................................63 
4.1 
CONFIDENTIALITY ..........................................................................................63 
4.2 
INSTITUTIONAL REVIEW ...............................................................................63 
4.3 
SUBJECT CONSENT ..........................................................................................63 
4.4 
STUDY REPORTING REQUIREMENTS ..........................................................64 
4.5 
FINANCIAL DISCLOSURE AND OBLIGATIONS ..........................................64 
4.6 
INVESTIGATOR DOCUMENTATION ..............................................................64 
4.7 
STUDY CONDUCT ............................................................................................65 
4.8 
DATA COLLECTION ..........................................................................................65 
4.8.1 
Case Report Forms and Source Documents .....................................................65 
4.9 
ADHERENCE TO PROTOCOL ..........................................................................66 
4.10 
REPORTING ADVERSE EVENTS ....................................................................66 
4.11 
INVESTIGATOR’S FINAL REPORT .................................................................66 
4.12 
RECORDS RETENTION ....................................................................................66 
4.13 
PUBLICATIONS ..................................................................................................67 
5. 
STUDY MANAGEMENT ......................................................................................68 
5.1 
MONITORING ....................................................................................................68 
5.1.1 
Monitoring of the Study ...................................................................................68 
5.1.2 
Inspection of Records .......................................................................................68 
5.2 
MANAGEMENT OF PROTOCOL AMENDMENTS AND DEVIATIONS ......68 
5.2.1 
Modification of the Protocol.............................................................................68 
5.2.2 
Protocol Deviations ..........................................................................................68 
5.3 
STUDY TERMINATION .....................................................................................69 
5.4 
FINAL REPORT ..................................................................................................69 
6. 
APPENDICES .........................................................................................................71 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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6.1 
APPENDIX 1: SCHEDULE OF EVENTS ..........................................................71 
6.2 
APPENDIX 2 - LIST OF EXAMPLE INHIBITORS AND INDUCERS OF 
CYP3A4 ...............................................................................................................74 
6.3 
APPENDIX 3 - INFUSION SITE ASSESSMENT .............................................75 
6.4 
APPENDIX 4: SECOND SYMPOSIUM ON THE DEFINITION AND 
MANAGEMENT OF ANAPHYLAXIS: SUMMARY REPORT—SECOND 
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS 
DISEASE/FOOD ALLERGY AND ANAPHYLAXIS NETWORK 
SYMPOSIUM ......................................................................................................76 
7. 
REFERENCE LIST................................................................................................77 
 
LIST OF TABLES 
Table 6–1 
Schedule of Events ...............................................................................................72 
 
LIST OF FIGURES 
Figure 3–1 
Study Flow Diagram ............................................................................................31 
 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 8 
PROTOCOL SYNOPSIS 
PROTOCOL NO.: PB2452-PT-CL-0001 
TITLE: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 
MEDI2452 (PB2452) With and Without Ticagrelor Pretreatment in Healthy Volunteers 
STUDY PHASE: 1 
STUDY SITE: 1 clinical site in the United States: PPD Phase 1 Clinic, 7551 Metro Center 
Drive, Suite 200, Austin, Texas 78744 
OBJECTIVES: 
Primary: 
• To evaluate the safety and tolerability of single ascending intravenous (IV) doses of 
MEDI2452 (PB2452) with or without oral ticagrelor 
• To evaluate the effectiveness of single ascending doses of MEDI2452 (PB2452) on 
ticagrelor antiplatelet activity by measuring inhibition of platelet activity (IPA) relative to 
predose ticagrelor using light transmittance aggregometry (LTA) 
Secondary: 
• To determine the pharmacokinetics of ascending doses of IV MEDI2452 (PB2452) in the 
presence and absence of ticagrelor 
• To determine the pharmacokinetics of ticagrelor and its active metabolite 
AR-C124910XX in the presence and absence of MEDI2452 (PB2452) 
• To assess the effectiveness of a single IV MEDI2452 (PB2452) dose in reversing 
ticagrelor antiplatelet activity by measuring P2Y12 reaction units (PRU) with 
VerifyNow™ P2Y12 assay and platelet reactivity index (PRI) with vasodilator stimulated 
phosphoprotein (VASP) phosphorylation assay by enzyme-linked immunosorbent assay 
(ELISA) 
• To evaluate the pharmacokinetics and pharmacodynamics of restarting a single dose of 
oral ticagrelor 24 hours after IV MEDI2452 (PB2452) administration 
• To evaluate the immunogenicity potential of MEDI2452 (PB2452) 
Exploratory: 
• To evaluate the effect of MEDI2452 (PB2452) on the pharmacokinetic (PK) profile of 
unbound ticagrelor and unbound AR-C124910XX plasma concentrations 
STUDY DESIGN AND METHODOLOGY: 
This is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled, single 
ascending dose, sequential group study to evaluate the safety, tolerability, pharmacokinetics, 
and pharmacodynamics of MEDI2452 (PB2452) with and without ticagrelor pretreatment 
when administered to healthy male and female subjects. 
Up to 6 dose levels will be evaluated. This study will have up to 9 cohorts and up to a total of 
approximately 60 subjects with either 4 or 8 subjects in each cohort depending on the dose. 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 9 
The starting dose of MEDI2452 (PB2452) will be 100 mg and the planned doses for 
subsequent cohorts are 300, 1000, 3000, 9000, and 18000 mg. 
The study will consist of a screening period (Days –28 to –4), check-in/pretreatment (Day -3 
to Day -1), an in-house treatment period (Days 1 through 3), and follow-up visits (Days 4, 7, 
and 28 [+2 days]). Subjects will receive an IV dose of MEDI2452 (PB2452) or placebo on 
Day 1. 
On Day 1, subjects who meet all of the inclusion criteria and none of the exclusion criteria 
will be randomly assigned to receive MEDI2452 (PB2452) or placebo in a ratio of 3:1 or 6:2 
in the following treatment cohorts: 
Cohorts 1 to 3: 
For the initial cohort (Cohort 1), 4 healthy subjects will be randomly assigned in a 3:1 ratio 
of active treatment to placebo (3A:1P) to receive a single 100-mg IV dose of MEDI2452 
(PB2452) or placebo over 30 minutes. For the second cohort (Cohort 2), 4 healthy subjects 
will be randomly assigned (3A:1P) to receive a single 300-mg IV dose of MEDI2452 
(PB2452) or placebo over 30 minutes. For the third cohort (Cohort 3), 4 healthy subjects will 
be randomly assigned (3A:1P) to receive a 1000-mg IV dose of MEDI2452 (PB2452) or 
placebo over 30 minutes. 
Cohorts 4 to 7: 
Provided no safety concerns arise in Cohorts 1 through 3, 8 subjects in each of Cohorts 4 
through 7 will be randomly assigned in a 6:2 ratio (6A:2P) to receive a single IV dose of 
MEDI2452 (PB2452) or placebo simultaneous with the 5th dose of ticagrelor pretreatment. 
For ticagrelor pretreatment, subjects will receive an oral loading dose of 180-mg ticagrelor in 
the morning (Day -2), followed by 90-mg ticagrelor orally every 12 hours for 4 additional 
doses, prior to administration of a single IV dose of MEDI2452 (PB2452) or placebo 
simultaneous with the 5th ticagrelor dose (Day 1). Subjects in each of Cohorts 4 through 7 
will receive ticagrelor pretreatment, as described above, and a single IV dose of 1000, 3000, 
9000, or 18000 mg of MEDI2452 (PB2452), respectively, or placebo over 30 minutes. 
Cohorts 4 through 7 will be dosed sequentially following the safety and dose-escalation 
assessment of each preceding dose cohort. 
Cohorts 8 and 9: 
For the final 2 dose cohorts (Cohorts 8 and 9), following ticagrelor pretreatment, subjects 
will be randomly assigned (6A:2P) to receive a single IV dose of 9000 or 18000 mg of 
MEDI2452 (PB2452), respectively, or placebo, and will also receive an additional single oral 
dose of 180-mg ticagrelor 24 hours after the initiation of the MEDI2452 (PB2452) or placebo 
infusion. Cohort 8 may be initiated following the safety and dose escalation assessment of 
Cohort 6 (9000-mg MEDI2452 [PB2452]), and Cohort 9 may be initiated following the 
safety and dose escalation assessment of Cohort 7 (18000-mg MEDI2452 [PB2452]). 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 10 
Cohort 
Pre-MEDI2452 
(PB2452) Ticagrelor 
dosing to steady state 
(180 mg + 90 mg bid 
for 5 doses total) 
MEDI2452 
(PB2452) 
Dose (mg) 
Post-MEDI2452 
(PB2452) 
Ticagrelor (180 mg) 
24 hours following 
MEDI2452 (PB2452) 
or placebo 
Number of subjects 
MEDI2452 
(PB2452):placebo 
1 
 
100 
 
3:1 
2 
 
300 
 
3:1 
3 
 
1000 
 
3:1 
4 
180 mg + 90 mg bid 
1000 
 
6:2 
5 
180 mg + 90 mg bid 
3000 
 
6:2 
6 
180 mg + 90 mg bid 
9000 
 
6:2 
7 
180 mg + 90 mg bid 
18000 
 
6:2 
8 
180 mg + 90 mg bid 
9000 
180 mg 
6:2 
9 
180 mg + 90 mg bid 
18000 
180 mg 
6:2 
Abbreviations: bid, twice daily 
Subjects in Cohorts 1 through 3 will check in to the clinical site on Day -1. On Day 1, 
subjects will receive a single IV dose of MEDI2452 (PB2452) or placebo in the morning. 
Subjects will undergo end-of-study (EOS) procedures and will be discharged from the 
clinical site on Day 3. Subjects will return for follow-up visits on Days 4, 7, and 28 
(+2 days). 
Subjects in Cohorts 4 through 9 will check in to the clinical site on Day -3. In the morning on 
Day -2, subjects will begin pretreatment with ticagrelor. On Day 1, simultaneous with the 
5th ticagrelor dose, subjects will receive a single IV dose of MEDI2452 (PB2452) or placebo 
in the morning. Subjects in Cohorts 4 through 7 will undergo EOS procedures and will be 
discharged from the clinical site on Day 3 and will return for follow-up visits on Days 4, 7, 
and 28 (+2 days). On Day 2, subjects in Cohorts 8 and 9 will receive an additional dose of 
ticagrelor in the morning 24 hours after the initiation of the MEDI2452 (PB2452) infusion 
and 5th ticagrelor dose. Subjects in Cohorts 8 and 9 will undergo EOS procedures and will be 
discharged from the clinical site on Day 4 and return for follow-up visits on Days 7 and 28 
(+ 2 days). 
Plasma samples for PK and pharmacodynamic (PD) analysis of MEDI2452 (PB2452), 
ticagrelor, and its active metabolite, AR-C124910XX, and urine samples for the PK analysis 
of ticagrelor and AR-C124910XX will be collected at specified intervals up to 28 days after 
dosing. Pharmacokinetic and PD samples will be obtained at identical time points; Hour 0 
will be the initiation of the MEDI2452 (PB2452) infusion (Cohorts 1 through 3) and the 
simultaneous administration of the MEDI2452 (PB2452) infusion and the 5th ticagrelor dose 
(Cohorts 4 through 9). 
Safety and tolerability will be carefully monitored throughout the study. Immunogenicity will 
be determined in all subjects at baseline and for up to 28 days following administration of 
MEDI2452 (PB2452). 
The estimated duration of the study for each subject, excluding screening, is approximately 
30 days. 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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Sentinel Dosing 
Dosing for Cohort 1 (first exposure of MEDI2452 [PB2452] in humans) will proceed with 
two sentinel subjects initially randomly assigned to receive a single IV dose of MEDI2452 
(PB2452) or placebo. Blinded safety data from the sentinel subjects up to 24-hours following 
the MEDI2452 (PB2452) or placebo dose will be reviewed by the investigator before the 
remaining 2 subjects in Cohort 1 are dosed. The remaining subjects will be dosed at least 
24 hours after the sentinel subjects. Additionally, dosing for Cohort 4 (first exposure of the 
combination of MEDI2452 [PB2452] with ticagrelor in humans) will proceed with 2 sentinel 
subjects pre-treated with ticagrelor prior to receiving a single IV dose of MEDI2452 
(PB2452) or placebo randomized in a 1:1 ratio of active to placebo. Blinded safety data from 
the sentinel subjects up to 24 hours following the ticagrelor and MEDI2452 (PB2452) or 
placebo dose will be reviewed by the investigator before the remaining 6 subjects in Cohort 4 
are dosed. The remaining subjects will be dosed at least 24 hours after the sentinel subjects. 
Dose Escalation 
A safety review committee (SRC) will be formed for blinded reviews of safety (eg, clinical 
laboratory results, adverse events [AEs], 12-lead electrocardiograms [ECGs], vital signs) and 
available PK data through Day 4 for each dose cohort. The SRC will be minimally composed 
of the on-site investigator, PPD medical monitor, and clinical pharmacologist, and the 
PhaseBio study director and clinical operations lead. Dose escalation to successive cohorts 
will be based upon safety of the preceding cohort. The investigator will make a 
recommendation on whether to proceed to the next predefined dose level, pause dosing for 
review of additional safety and/or PK data, or to adjust the dose of the next dose cohort. The 
decision to adjust or pause the dose or proceed to the next cohort will be made by the SRC. 
The safety data will be reviewed in a blinded manner and must be deemed acceptable to the 
SRC prior to dosing of the next higher dose group. 
Based on the review of safety and PK data, if available, the SRC may choose to repeat a dose 
level, administer a dose less than the previous dose, or escalate to a dose lower than the next 
planned dose. 
Stopping Criteria 
After completion of Day 4 for each dose cohort, the SRC will review and assess all available 
safety (eg, clinical laboratory results, AEs, ECGs, vital signs), tolerability, and available PK 
data to make a decision on the dose for next dose cohort. Dose escalation may be suspended 
if any of the following scenarios occur with a reasonable possibility of causal relationship 
with MEDI2452 (PB2452): 
• Events that, in the opinion of the medical monitor and SRC, contraindicate further dosing 
of additional subjects 
• Any serious adverse event with a suspected relationship to MEDI2452 (PB2452) in a 
dose cohort 
• Data from a previous dose cohort indicating safety concerns for the next cohort to be 
dosed at a higher level, such as unanticipated responses (eg, clinically significant changes 
in clinical laboratory data, ECGs, cardiac telemetry, vital signs, or physical examinations) 
• More than 50% of the subjects in a given dose cohort are withdrawn due to poor 
tolerability of MEDI2452 (PB2452) 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 12 
• Two or more subjects experiencing severe AEs assessed at least possibly related to 
MEDI2452 (PB2452), or 1 or more subjects experiencing severe AEs at least possibly 
related to MEDI2452 (PB2452) at the discretion of the investigator 
• Two or more subjects have > 3 × upper limit of normal (ULN) of either alanine 
aminotransferase or aspartate aminotransferase, or > 2 × ULN for bilirubin or alkaline 
phosphatase where no other reason can be found to explain the combination of increases 
• Two or more subjects experiencing a severe infusion reaction 
Dose escalation may also be suspended if, in the opinion of the investigator or sponsor, any 
other significant safety or tolerability issues are identified in the comprehensive review of 
available data that warrant further evaluation before additional subjects are dosed. This may 
include emerging nonclinical data, clinically relevant AEs, or relevant data from other 
sources indicating safety concerns even if the event(s) per se does not meet the 
protocol-specified definition of a dose-limiting toxicity. 
INCLUSION CRITERIA: 
1. The subject is male or female between 18 and 50 years of age, inclusive. 
2. The subject has a body mass index between 18 and 35 kg/m2 and a weight of ≥50 kg but 
≤120 kg, inclusive, at screening. 
3. The subject is considered by the investigator to be in good general health as determined 
by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG 
results, and physical examination findings at screening. 
4. Female subjects of childbearing potential must not be pregnant, lactating, or planning to 
become pregnant before 3 months after the last dose of study drug, and have a negative 
serum pregnancy test at screening and check-in. Female subjects of childbearing potential 
must use 2 effective methods of birth control (ie, oral, implantable, patch, or injectable 
contraceptives in combination with a condom, hormone-containing intrauterine device 
that has been in place for at least 2 months prior to screening in combination with a 
condom, double-barrier method [ie, condoms, sponge, diaphragm, or cervical cap with 
spermicidal gels or cream], or vasectomy for male subjects or male partners of female 
subjects) from 30 days before study drug administration through the end of the study. 
Women are considered not to be of childbearing potential if they have fulfilled one of the 
following criteria: documentation of irreversible surgical sterilization (ie, hysterectomy, 
or bilateral oophorectomy [not tubal ligation]), or postmenopausal (defined as 
amenorrhea for 12 consecutive months following cessation of all exogenous hormonal 
treatments, and documented plasma follicle-stimulating hormone level >40 IU/mL). Male 
subjects with partners of childbearing potential must agree to use appropriate and 
effective measures of contraception (eg, condom plus diaphragm with spermicide; 
condom plus spermicide) during the study and for 30 days after the last dose of study 
drug, and to refrain from donating sperm for at least 7 days prior to the first dose of study 
drug and until at least 90 days following the last dose of study drug. 
5. The subject agrees to comply with all protocol requirements. 
6. The subject is able to provide written informed consent. 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 13 
EXCLUSION CRITERIA: 
1. History of any clinically significant disease or disorder which, in the opinion of the 
investigator, may either put the subject at risk because of participation in the study, or 
influence the results or the subject’s ability to participate in the study. 
2. History or presence of gastrointestinal, hepatic, or renal disease (with the exception of 
Gilbert’s syndrome) or renal insufficiency (ie, estimated glomerular filtration rate 
<60 ml/min/1.73m2), or any other condition known to interfere with absorption, 
distribution, metabolism, or excretion of drugs. 
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks 
of the first administration of study drug. 
4. Any clinically relevant abnormal findings in physical examination, vital signs, 
hematology and coagulation parameters, clinical chemistry, or urinalysis results during 
screening or check-in, which in the opinion of the investigator or medical monitor may 
compromise the safety of the subject in the study or interfere with the evaluation of the 
study drug or reduce the subjects’ ability to participate in the study. Specific exclusionary 
values at screening or check-in blood tests are any of the following: 
• Aspartate transaminase level >1.5 × ULN 
• Alanine transaminase level >1.5 × ULN 
• Hemoglobin level below the lower limit of normal (hemoglobin levels within 
0.5 g/L of the lower cut off point may be acceptable based on the judgment of the 
investigator and medical monitor) 
• Thyroid stimulating hormone level above the ULN at screening 
• Prothrombin time or partial thromboplastin time level outside the normal range 
5. The subject has an increased risk of bleeding, including the following: 
• Recent history (within 30 days preceding the first dose of study drug) of 
gastrointestinal bleeding 
• Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding 
• Any recent (within 30 days preceding the first dose of study drug) major trauma 
• History of hemorrhagic disorders that may increase the risk of bleeding (eg, 
hemophilia, von Willebrand’s disease) 
• Inability to discontinue therapy with nonsteroidal anti-inflammatory drugs at 
screening (must discontinue medication within at least 7 days or 5 half-lives, 
whichever is longer, prior to first dose of study drug) 
• Subjects who have taken, within 30 days of screening, any oral or parenteral 
anticoagulant, including low molecular-weight heparin 
• Platelet count <100,000 mm3  
6. Any clinically important abnormalities in rhythm, conduction, or morphology of the 
resting 12-lead ECG or any abnormalities that may interfere with the interpretation of 


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MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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serial ECG changes, including corrected QT interval (QTc) interval changes at screening, 
as judged by the investigator, and also including: 
• Prolonged Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec), 
shortened QTcF <340 msec, or pause >3 seconds at screening, or family history of 
long QT syndrome 
• Prolonged PR (PQ) interval >240 msec, intermittent second- or third-degree 
atrioventricular (AV) block or AV dissociation, or shortened PR interval 
<120 msec at screening 
• Incomplete, full, or intermittent bundle branch block (QRS <110 msec with 
normal QRS and T wave morphology is acceptable if there is no evidence of left 
ventricular hypertrophy) 
7. The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus 
antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening. 
8. Abnormal vital signs after 10 minutes supine rest, defined as any of the following: 
• Systolic blood pressure >140 mm Hg 
• Diastolic blood pressure >90 mmHg 
• Heart rate <50 or >100 beats per minute 
Note: Abnormal results may be repeated once for confirmation, at the discretion of 
the investigator. 
9. The subject should not participate in the study if they have any ongoing or recent (ie, 
during the screening period) minor medical complaints that may interfere with the 
interpretation of the study data or are considered unlikely to comply with study 
procedures, restrictions, and requirements as judged by the investigator. 
10. History of transient ischemic attack or cardiovascular accident (ischemic or 
hemorrhagic), severe head trauma, intracranial hemorrhage, intracranial neoplasm, 
arteriovenous malformation, aneurysm, or proliferative retinopathy. 
11. The subject is receiving chronic treatment with nonsteroidal anti-inflammatory drugs 
(including aspirin [greater than 100 mg daily]), anticoagulants, or other antiplatelet 
agents that cannot be discontinued (including clopidogrel, prasugrel, ticlopidine, 
dipyridamole, or cilostazol). 
12. The subject is considered to be at risk of bradycardic events (eg, known sick sinus 
syndrome, atrial fibrillation, or second- or third-degree AV block) unless already treated 
with a pacemaker. 
13. Concomitant oral or IV therapy with strong CYP3A inhibitors, CYP3A substrates with 
narrow therapeutic indices, or strong CYP3A inducers, which cannot be stopped within at 
least 5 half-lives, but not shorter than 10 days, before randomization (a list of examples 
can be found in Section 6.2). 


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14. The subject has used any prescription (excluding hormonal birth control) or 
over-the-counter medications (except paracetamol [up to 2 g per day]), including herbal 
or nutritional supplements, within 14 days before the first dose of study drug. 
15. The subject has consumed grapefruit or grapefruit juice, Seville orange or Seville 
orange-containing products (eg, marmalade), or alcohol-, or xanthine-containing products 
within 48 hours before dosing with study drug. 
16. The subject is participating in any other study or is taking part in a non-medication study 
which, in the opinion of the investigator, would interfere with the outcome of the study. 
17. The subject has received another new chemical entity (defined as a compound which has 
not been approved for marketing) or any marketed or investigational biologic agent 
within 30 days of the first administration of study drug in this study. The period of 
exclusion begins 30 days after the final dose or 5 half-lives of the experimental 
medication has elapsed, whichever is longer. 
18. The subject has involvement with any PhaseBio or study site employee or their close 
relatives (eg, spouse, parents, siblings, or children whether biological or legally adopted). 
19. The subject has previously received MEDI2452 (PB2452). 
20. The subject is a smoker or has used nicotine or nicotine-containing products (eg, snuff, 
nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months 
before the first dose of study drug. 
21. The subject has a known or suspected history of drug abuse (including alcohol) as judged 
by the investigator. 
22. The subject has a positive test result for drugs of abuse, alcohol, or cotinine (nicotine 
level above 300 ng/mL) at screening or check-in. 
23. The subject has a planned surgical procedure that will occur during the study (from 
screening through EOS). 
24. The subject is involved in strenuous activity or contact sports within 24 hours before the 
first dose of study drug and while confined in the clinical site. 
25. The subject has donated blood or plasma within 1 month of screening or any blood 
donation/loss more than 500 mL during the 3 months prior to the first dose of study drug. 
26. The 
subject 
has 
a 
history 
of 
severe 
allergy/hypersensitivity 
or 
ongoing 
allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to 
drugs with a similar chemical structure or class to ticagrelor, any biologic therapeutic 
agent, or any significant food allergy that could preclude a standard diet in the clinical 
site. 
27. Concern for the inability of the subject to comply with study procedures and/or 
follow-up, or, in the opinion of the investigator, the subject is not suitable for entry into 
the study. 


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MEDI2452 (PB2452) 
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EVALUATION CRITERIA: 
Safety Assessments: 
Safety and tolerability will be assessed by monitoring and recording of AEs, clinical 
laboratory test results (hematology, coagulation, serum chemistry, and urinalysis), vital sign 
measurements (systolic and diastolic blood pressures, oral body temperature, respiratory rate, 
and heart rate), 12-lead ECG results, cardiac telemetry monitoring, immunogenicity, and 
physical examination findings. 
Pharmacokinetic Assessments: 
Plasma Collection: 
Blood samples for PK analysis of MEDI2452 (PB2452) in serum will be collected from all 
subjects at the following time points: before dosing (Hour 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 
12, 24, 48, and 72 hours, and at 7 and 28 days after initiation of the MEDI2452 (PB2452) 
infusion. 
Plasma samples for determining total concentrations of ticagrelor and its active metabolite, 
AR-C124910XX, will be collected from subjects in Cohorts 4 through 9 at the following 
timepoints: before dosing (within 10 minutes prior to the initiation of MEDI2452 [PB2452] 
infusion and 5th ticagrelor dose [Hour 0]), and at 0.5, 1, 2, 3, 6, 12, and 24 hours after the 
initiation of the MEDI2452 (PB2452) infusion and 5th ticagrelor dose. Additional samples 
will be collected from subjects in Cohorts 8 and 9 at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after 
the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. 
Plasma samples for determining unbound ticagrelor and AR-C124910XX concentrations will 
be collected from subjects in Cohorts 4 through 9 at the following timepoints: before dosing 
(within 10 minutes prior to the initiation of MEDI2452 [PB2452] infusion and 5th ticagrelor 
dose [Hour 0]), and at 0.5, 1, 2, 3, 6, 12, and 24 hours after the initiation of the MEDI2452 
(PB2452) infusion and 5th ticagrelor dose. Additional samples will be collected from subjects 
in Cohorts 8 and 9 at 0.5, 1, 2, 3, 6, 12, and 24 hours after the Day 2 post-MEDI2452 
(PB2452) 6th ticagrelor dose. 
The following plasma PK parameters for MEDI2452 (PB2452) will be calculated: 
• Area under the plasma concentration versus time curve (AUC) from time 0 to the time of 
the last quantifiable concentration (AUC0-t) 
• Observed maximum plasma concentration (Cmax) 
• Time to reach the observed maximum plasma concentration (Tmax) 
• AUC from time 0 extrapolated to infinity (AUC0-inf) (if data permit) 
• Terminal elimination half-life (t½) (if data permit) 
• Apparent clearance (CL) (if data permit) 
The following plasma PK parameters for ticagrelor and AR-C124910XX will be calculated: 
• Cmax 
• Tmax 
• AUC from time 0 to 12 hours after dosing (AUC0-12) 
• AUC from time 0 to 24 hours after dosing (AUC0-24) 


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Protocol No. PB2452-PT-CL-0001 
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• AUC0-inf (if data permit) 
• t½ (if data permit) 
The following plasma PK parameters for the metabolite AR-C124910XX will be calculated: 
• Cmax ratio (metabolite:parent) 
• AUC0-24 ratio (metabolite:parent) 
Urine Collection: 
Pooled urine samples to assess urine ticagrelor and AR-C124910XX concentrations will be 
collected from subjects in Cohorts 4 through 9 over the following intervals: before dosing 
(within 60 minutes prior to the first ticagrelor dose on Day -2) and 0 to 6, 6 to 12, and 12 to 
24 hours after the initiation of the MEDI2452 (PB2452) infusion and 5th ticagrelor dose. 
The following PK parameters for ticagrelor and AR-C124910XX concentrations in urine will 
be calculated: 
• Total amount of drug excreted in urine (Ae) 
• Ae from time t1 to t2 hours where the values of t1 to t2 are 0 to 6, 6 to 12, and 12 to 24 
(Aet1-t2) 
• Fraction excreted in urine from 1 to 24 hours after dosing (Fe) 
• Renal clearance (CLr) 
Additional PK parameters may be generated, if needed. 
Pharmacodynamic Assessments: 
Blood samples for PD analysis will be collected from subjects in Cohorts 4 through 9 at the 
following time points: before dosing (within 60 minutes prior to first ticagrelor dose on 
Day -2) and again before dosing (within 10 minutes prior to the initiation of the MEDI2452 
[PB2452] infusion and 5th ticagrelor dose [Hour 0]), and at 0.5, 1, 2, 3, 6, 12, 24, and 
48 hours after the initiation of the MEDI2452 (PB2452) infusion and 5th ticagrelor dose. 
Additional samples will be collected from subjects in Cohorts 8 and 9 at 1, 2, 6, and 12 hours 
after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. 
The following PD parameters will be calculated using the data generated by LTA, P2Y12 
reaction units (PRU), and platelet reactivity index (PRI) assays: 
LTA: 
• Inhibition of platelet aggregation (IPA) (max and final extent) induced by 20µM 
adenosine diphosphate (ADP) at each assessment point 
• inhibition of maximal platelet aggregation (IPAmax) 
• time to IPAmax (TIPAmax) 
VerifyNow™P2Y12: 
• PRU at each assessment point 
VASP by ELISA: 
• PRI at each assessment point 
Additional PD parameters may be generated, if needed. 


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Protocol No. PB2452-PT-CL-0001 
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Immunogenicity: 
Blood samples will be screened for the presence of binding anti-drug antibodies (ADA) at 
check-in and on Days 7 and 28. 
STUDY DRUG, DOSAGE, AND ROUTE OF ADMINISTRATION: 
MEDI2452 (PB2452): 
All cohorts: MEDI2452 (PB2452) (concentration will vary between 0.4 mg/mL up to 
72 mg/mL) single IV infusion, 250 mL to be delivered over 30 minutes in escalating doses of 
100, 300, 1000, 3000, 9000, or 18000 mg 
Matching Placebo: 
All cohorts: 0.9% sodium chloride single IV infusion, 250 mL to be delivered over 
30 minutes 
Ticagrelor: 
Cohorts 4 through 9: ticagrelor 90-mg oral tablet (immediate release); administered as 
180 mg (2 × 90-mg tablet) loading dose plus 90 mg every 12 hours for 4 additional doses 
Cohorts 8 and 9: ticagrelor 90-mg oral tablet (immediate release); one additional dose 
administered as 180 mg (2 × 90-mg tablet) 24 hours after the initiation of the MEDI2452 
(PB2452) infusion 
STATISTICAL METHODS: 
Sample Size: 
The sample size (N = 60) for this study is based on clinical and practical considerations and 
not on a formal statistical power calculation. The sample size is considered sufficient to 
effectively assess the safety, PK, and PD profiles of MEDI2452 (PB2452) and the PK and PD 
profiles of ticagrelor. 
Analysis Populations: 
• The Safety population will include all subjects who receive any amount of study drug. 
• The PK population will include subjects who receive at least 1 dose of study drug and 
have at least 1 measurable PK concentration. 
• The PD population will include subjects who receive at least 1 dose of ticagrelor and 
have at least 1 measurable post dose LTA value. 
Safety Analyses: 
Adverse events will be coded by preferred term and system organ class using the latest 
version of the Medical Dictionary for Regulatory Activities. All AE data will be presented in 
a data listing. Treatment-emergent AEs will be summarized by treatment and overall, as well 
as by severity and relationship to study drug. Serious AEs and AEs leading to discontinuation 
of study drug will be presented in the data listings. 
Actual values and changes from baseline for clinical laboratory test results, vital sign 
measurements, and 12-lead ECG results will be summarized by treatment at each time point 
using descriptive statistics (number of subjects, mean, SD, median, minimum, and 
maximum). Clinical laboratory test results, vital sign measurements, 12-lead ECG results, 
immunogenicity results, and physical examination findings will be presented in data listings. 


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Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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Pharmacokinetic Analyses: 
Plasma concentrations will be listed and summarized descriptively (number of subjects, 
arithmetic mean, SD, coefficient of variation [CV], median, minimum, and maximum). 
Plasma/serum concentration versus time profiles for each subject will be presented 
graphically. The mean plasma/serum concentration versus scheduled time profiles will be 
presented graphically by dose. 
Pharmacokinetic parameters will be summarized by time point for each dose level using 
descriptive statistics (number of subjects, mean, SD, CV, median, minimum, and maximum). 
Geometric means will be reported for AUCs and Cmax. 
Dose proportionality will be tested using the power regression model for AUC0-inf, AUC0-t, 
and Cmax of MEDI2452 (PB2452) in Cohorts 4, 5, 6, and 7. 
Pharmacodynamic Analyses: 
Pharmacodynamic data will be summarized for each time point using descriptive statistics 
(number of subjects, mean, SD, CV, median, minimum, and maximum). Pharmacodynamic 
parameters will also be summarized for each dose level. 
Interim Analyses: 
A formal unblinded interim analysis (IA) of all accumulated safety, PD, and PK data (as 
needed) will be performed after the last subject in Cohort 6 completes follow-up visit Day 7 
to provide an interim assessment of the safety profile of MEDI2452 (PB2452) after the target 
efficacious dose level has been tested (Cohort 6). Pharmacodynamic and PK data analysis 
will also be included as needed in the IA to provide an assessment of the likely benefit/risk 
profile of the study drug. The prespecified IA analyses will be a subset of the final study 
analyses. The detailed scope of interim analyses will be outlined in a separate document, the 
statistical analysis plan (SAP). An independent statistical group will produce the interim 
analysis. 
DATE OF PROTOCOL: 01 Feb 2018 


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Protocol No. PB2452-PT-CL-0001 
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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACS 
acute coronary syndrome 
ADA 
anti-drug antibodies 
ADP 
adenosine diphosphate 
Ae 
total amount of drug excreted in urine 
Aet1-t2 
total amount of drug excreted in urine from time t1 to t2 hours where 
the values of t1 to t2 are 0 to 6, 6 to 12, and 12 to 24 
AE 
adverse event 
ALT 
alanine aminotransferase 
ASA 
acetylsalicylic acid 
AUC 
area under the plasma concentration versus time curve 
AUC0-12 
AUC from time 0 to 12 hours after dosing 
AUC0-24 
AUC from time 0 to 24 hours after dosing 
AUC0-inf 
area under the plasma concentration versus time curve from time 0 
extrapolated to infinity 
AUC0-t 
area under the concentration versus time curve from time 0 to the time 
of the last quantifiable concentration 
AUEC 
area under the effect curve 
AV 
atrioventricular 
BLQ 
below the limit of quantification 
CFR 
Code of Federal Regulations 
CL 
apparent clearance 
CLr 
renal clearance 
Cmax 
observed maximum plasma concentration 
CV 
coefficient of variation 
DAPT 
dual antiplatelet therapy 
DLT 
dose-limiting toxicity 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ELISA 
enzyme-linked immunosorbent assay 
Emax 
maximum observed concentrations or activity levels 
EOS 
end-of-study 
FDA 
Food and Drug Administration 
Fe 
fraction excreted in urine from 1 to 24 hours after dosing 
IA 
interim analyses 


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Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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Abbreviation 
Definition 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IPA 
inhibition of platelet aggregation 
IPAmax 
inhibition of maximal platelet aggregation 
IRB 
institutional review board 
IV 
intravenous 
IVSS 
intravenous stabilizing solution 
LTA 
light transmittance aggregometry 
Millisecond 
msec 
MTD 
maximum tolerated dose 
NOAEL 
no-observed-adverse-effect level 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
PRI 
platelet reactivity index 
PRU 
P2Y12 reaction units 
QTc 
corrected QT interval 
QTcF 
Fridericia-corrected QT interval 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SRC 
safety review committee 
t1/2 
terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
TIPAmax 
time to inhibition of maximal platelet aggregation 
Tmax 
time to reach the observed maximum (peak) concentration 
ULN 
upper limit of normal 
VASP 
vasodilator stimulated phosphoprotein 
 


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Protocol No. PB2452-PT-CL-0001 
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1. 
INTRODUCTION 
1.1 
BACKGROUND INFORMATION 
MEDI2452 (PB2452) is a specific and selective neutralizing antibody fragment that binds 
ticagrelor and AR-C124910XX, the major active circulating ticagrelor metabolite, with high 
affinity. MEDI2452 (PB2452) is intended to reverse the antiplatelet effects of ticagrelor in 
patients who experience major bleeding or who require urgent surgery or intervention, 
serious but rare conditions that represent an unmet medical need. 
Ticagrelor is an orally available, direct-acting cyclopentyltriazolopyrimidine, a selective and 
reversibly binding P2Y12 receptor antagonist (van Giezen et al 2009). AR-C124910XX, the 
ticagrelor active metabolite (30% to 40% plasma exposure relative to parent in humans 
(Storey et al 2007), has potency similar to that of ticagrelor versus P2Y12. In addition to 
P2Y12, ticagrelor also inhibits the equilibrative nucleoside transporter-1, thereby providing an 
enhanced adenosine response (Armstrong et al 2014, Cattaneo et al 2014). Ticagrelor in 
combination with low-dose aspirin (acetylsalicylic acid; ASA) is indicated for the prevention 
of thrombotic events (cardiovascular death, myocardial infarction, and stroke) in patients 
with acute coronary syndrome (ACS) or a history of myocardial infarction. Ticagrelor also 
reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. 
In the management of ACS, ticagrelor treatment is initiated with a 180-mg loading dose, 
followed by 90 mg twice daily during the first year after an ACS event. After one year the 
prescribed dosage is 60 mg twice daily. 
Therapy with ASA plus an oral antiplatelet agent such as clopidogrel, prasugrel, or ticagrelor 
is known as dual antiplatelet therapy (DAPT). While DAPT is strongly recommended in the 
early management of patients experiencing an ACS event, it also increases the risk of 
bleeding (Storey 2011). Patients with ACS may require urgent or emergent coronary artery 
bypass graft surgery. In such patients, DAPT is associated with a 2-fold increase in the risk of 
blood transfusion, a 5-fold increase in the risk of reoperation, and a 50% increased risk of 
wound infection (Bell et al 2011, Fitchett et al 2011). Consequently, guidelines and guidance 
statements recommend that the P2Y12 receptor antagonist be stopped at least 5 days prior to 
the procedure, a recommendation that is not possible to follow in patients who require urgent 
surgery. 
There are no approved drugs or biological agents capable of reversing the P2Y12 inhibition 
produced by ticagrelor or other P2Y12 inhibitors, and thus if a major bleeding event occurs in 
a patient on DAPT, there are limited treatment options. Although platelet transfusion restores 
platelet function in patients on ASA (Taylor et al 2013), it does not reverse the antiplatelet 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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effect of ticagrelor in healthy volunteers and is unlikely to be of clinical benefit in patients 
with bleeding (Teng et al 2016). The lack of an effective therapy to mitigate 
ticagrelor-induced platelet inhibition in patients who have life-threatening bleeding or require 
urgent surgery or intervention therefore represents a significant unmet need. 
MEDI2452 (PB2452) (molecular weight 47.4 kDa) is a recombinant human IgG1λ 
monoclonal fragment antigen-binding antibody that binds specifically to ticagrelor and 
AR-C124910XX. It is expressed in Escherichia coli cells. 
1.1.1 
Non-clinical Pharmacology 
Detailed descriptions of the non-clinical pharmacology of MEDI2452 (PB2452) may be 
found in the Investigator Brochure for MEDI2452 (PB2452). The key non-clinical 
pharmacology study findings for MEDI2452 (PB2452) are as follows: 
• MEDI2452 (PB2452) binds ticagrelor and its active metabolite, AR-C124910XX, 
selectively and with a high affinity (equilibrium dissociation constant [KD] 20 pmol/L). 
• MEDI2452 (PB2452) rapidly neutralizes the unbound plasma fraction of ticagrelor and 
AR-C124910XX and thereby reverses ticagrelor- and AR-C124910XX-mediated 
inhibition of adenosine diphosphate (ADP)-induced platelet aggregation in a 
concentration- and dose-dependent manner in vitro (in human platelet-rich plasma) and in 
vivo (mouse and pig, dose-dependency data in mouse only). 
• In mice dosed with ticagrelor to a supratherapeutic plasma exposure, MEDI2452 
(PB2452) dosed before a tail cut reduced bleeding to a level that was not statistically 
different from that observed in mice not treated with ticagrelor. 
• In pigs dosed to a supratherapeutic ticagrelor exposure on a background of ASA, 
MEDI2452 (PB2452) dosed after liver injury induced an elimination of free ticagrelor 
and AR-C124910XX in plasma within 5 minutes. The elimination translated into a 
gradual reversal of ticagrelor-mediated inhibition of ADP-induced platelet aggregation 
and numerical, but nonsignificant, improvements in mean arterial pressure, blood loss, 
and survival. 
Non-clinical pharmacology studies have demonstrated that MEDI2452 (PB2452) binds with 
high affinity and selectivity to the P2Y12 receptor antagonist ticagrelor and its active 
metabolite AR-C124910XX. MEDI2452 (PB2452) produces concentration (dose)-dependent 
reversal of ticagrelor- and AR-C124910XX-mediated inhibition of ADP-induced platelet 
aggregation. The activity in vitro and the rapid onset of effect observed in vivo translated to a 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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reduction of bleeding in ticagrelor-treated mice to a level that was not statistically different 
from that observed in mice not treated with ticagrelor. 
1.1.2 
Benefit/Risk Assessment 
Healthy volunteers are not expected to receive any benefit from administration of MEDI2452 
(PB2452). In patients who are taking ticagrelor and who experience serious bleeding or who 
require emergency or urgent surgical procedures, MEDI2452 (PB2452) may provide 
significant clinical benefit by reversing the ticagrelor antiplatelet effect and thereby 
promoting hemostasis. 
The potential risks of infusion site reactions and hypersensitivity-type reactions are generic 
for recombinant protein drugs administered intravenously. These risks can be mitigated by 
predefined exclusion criteria and by close monitoring during and after administration. 
In patients taking ticagrelor for therapeutic benefit, the potential risk of thrombosis upon 
reversal of the antiplatelet effect of ticagrelor will be evaluated in future clinical studies and 
by thorough monitoring of hemostasis parameters. 
Based on available information regarding the risks of MEDI2452 (PB2452) and the 
precautions included in this first clinical study, the risks are considered acceptable. 
1.2 
RATIONALE FOR STUDY 
This is the first-in-human study with MEDI2452 (PB2452) and is designed to provide initial 
safety, tolerability, pharmacokinetics, and pharmacodynamics data regarding MEDI2452 
(PB2452) for future clinical studies. 
Current recommendations for management of bleeding in patients treated with antiplatelet 
therapies are suboptimal because they are mostly supportive and non-specific. Platelet 
transfusion, while useful for some antiplatelet agents, exposes patients to the known risks of 
blood products, and the efficacy of transfused platelets may be limited by exposure to 
circulating antiplatelet drug or metabolites if present. Moreover, it has been demonstrated 
that platelet transfusions do not reverse the effects of ticagrelor (Dalen et al 2013, 
Godier et al 2015, Maillard et al 2015, Teng et al 2016). 
The availability of an agent that reduces the inhibition of platelet aggregation associated with 
ticagrelor and AR-C124910XX would fulfill an important unmet clinical need for the 
following patient populations: 


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• Patients with major bleeding where ticagrelor may be contributing 
• Patients taking ticagrelor who require urgent surgery or intervention associated with a 
high risk of bleeding 
• Patients taking ticagrelor for conditions with a high risk of thrombosis who require major 
surgery and for whom it is deemed important to minimize the time during which they are 
not using ticagrelor 
1.3 
RATIONALE FOR DOSE SELECTION 
There were no adverse effects following a single dose of MEDI2452 (PB2452) given 
intravenously to rats, alone or in combination with oral ticagrelor (20 mg/kg), at doses up to 
2000 mg/kg. Therefore, 2000 mg/kg of MEDI2452 (PB2452) was considered to be the no 
adverse effect level (NOAEL) (systemic exposures Cmax 18100 µg/mL, AUC(0-inf) 
23100 µg*h/mL). 
The recommended dose of MEDI2452 (PB2452) for clinical use will be that sufficient to 
neutralize total body ticagrelor at steady state in a patient using ticagrelor 90 mg twice daily. 
The doses to be investigated in Phase I were determined using pharmacokinetic 
(PK)/pharmacodynamic (PD) modeling. In brief, a MEDI2452 (PB2452) dose of 100 mg at 
10-fold lower than the expected minimally pharmacologically active dose of 1000 mg is 
proposed as the starting dose, with a first escalation to 300 mg. Allowing for an escalation of 
up to 3-fold in each ascending-dose cohort, doses of MEDI2452 (PB2452) to be tested in the 
presence of ticagrelor are 1000, 3000, and 9000 mg with a higher dose cohort of 18000 mg to 
provide safety and tolerability and PK/PD information at higher exposures. 
The maximum dose that will be administered in this initial Phase 1 study is 18000 mg. The 
safety margin at the maximum proposed human dose of 18000 mg is 0.6 based on the 
NOAEL AUC in the pivotal rat Good Laboratory Practice toxicity study in which no adverse 
effects of single doses of MEDI2452 (PB2452) intravenously administered alone or in 
combination with oral ticagrelor were observed at the highest dose level tested (2000 mg/kg, 
NOAEL). 


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2. 
STUDY OBJECTIVES 
2.1 
PRIMARY OBJECTIVES 
The primary objectives of this study are: 
• To evaluate the safety and tolerability of single ascending intravenous (IV) doses of 
MEDI2452 (PB2452) with or without ticagrelor 
• To evaluate the effectiveness of single ascending doses of MEDI2452 (PB2452) dose on 
ticagrelor antiplatelet activity by measuring inhibition of platelet activity (IPA) relative to 
predose ticagrelor using light transmittance aggregometry (LTA) 
2.2 
SECONDARY OBJECTIVES 
The secondary objectives of the study are: 
• To determine the pharmacokinetics of ascending doses of IV MEDI2452 (PB2452) in the 
presence and absence of ticagrelor 
• To determine the pharmacokinetics of ticagrelor and its active metabolite 
AR-C124910XX in the presence and absence of MEDI2452 (PB2452) 
• To assess the effectiveness of a single IV MEDI2452 (PB2452) dose in reversing 
ticagrelor antiplatelet activity by measuring P2Y12 reaction units (PRU) with 
VerifyNow™ P2Y12 assay and platelet reactivity index (PRI) with vasodilator stimulated 
phosphoprotein (VASP) phosphorylation assay by enzyme-linked immunosorbent assay 
(ELISA) 
• To evaluate the pharmacokinetics and pharmacodynamics of restarting a single dose of 
oral ticagrelor 24 hours after MEDI2452 (PB2452) administration 
• To evaluate the immunogenicity potential of MEDI2452 (PB2452) 
2.3 
EXPLORATORY OBJECTIVE 
The exploratory objective of the study is: 
• To evaluate the effect of MEDI2452 (PB2452) on the PK profile of unbound ticagrelor 
and unbound AR-C124910XX plasma concentrations 


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3. 
INVESTIGATIONAL PLAN 
3.1 
STUDY DESIGN 
This is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled, single 
ascending dose, sequential group study to evaluate the safety, tolerability, pharmacokinetics, 
and pharmacodynamics of MEDI2452 (PB2452) with and without ticagrelor pretreatment 
when administered to healthy male and female subjects. 
Up to 6 dose levels will be evaluated. This study will have up to 9 cohorts and up to a total of 
approximately 60 subjects with either 4 or 8 subjects in each cohort depending on the dose. 
The starting dose of MEDI2452 (PB2452) will be 100 mg and the planned doses for 
subsequent cohorts are 300, 1000, 3000, 9000, and 18000 mg. 
The study will consist of a screening period (Days –28 to –4), check-in/pretreatment (Day -3 
to Day -1), an in-house treatment period (Days 1 through 3), and follow-up visits (Days 4, 7, 
and 28 [+2 days]). Subjects will receive an IV dose of MEDI2452 (PB2452) or placebo on 
Day 1. 
On Day 1, subjects who meet all of the inclusion criteria and none of the exclusion criteria 
will be randomly assigned to receive MEDI2452 (PB2452) or placebo in a ratio of 3:1 or 6:2 
in the following treatment cohorts: 
Cohorts 1 to 3: 
For the initial cohort (Cohort 1), 4 healthy subjects will be randomly assigned in a 3:1 ratio 
of active treatment to placebo (3A:1P) to receive a single 100-mg IV dose of MEDI2452 
(PB2452) or placebo over 30 minutes. For the second cohort (Cohort 2), 4 healthy subjects 
will be randomly assigned (3A:1P) to receive a single 300-mg IV dose of MEDI2452 
(PB2452) or placebo over 30 minutes. For the third cohort (Cohort 3), 4 healthy subjects will 
be randomly assigned (3A:1P) to receive a 1000-mg IV dose of MEDI2452 (PB2452) or 
placebo over 30 minutes. 
Cohorts 4 to 7: 
Provided no safety concerns arise in Cohorts 1 through 3, 8 subjects in each of Cohorts 4 
through 7 will be randomly assigned in a 6:2 ratio (6A:2P) to receive a single IV dose of 
MEDI2452 (PB2452) or placebo simultaneous with the 5th dose of ticagrelor pretreatment. 
For ticagrelor pretreatment, subjects will receive an oral loading dose of 180-mg ticagrelor in 
the morning (Day -2), followed by 90-mg ticagrelor orally every 12 hours for 4 additional 
doses, prior to administration of a single IV dose of MEDI2452 (PB2452) or placebo 


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MEDI2452 (PB2452) 
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simultaneous with the 5th ticagrelor dose (Day 1). Subjects in each of Cohorts 4 through 7 
will receive ticagrelor pretreatment, as described above, and a single IV dose of 1000, 3000, 
9000, or 18000 mg of MEDI2452 (PB2452), respectively, or placebo over 30 minutes. 
Cohorts 4 through 7 will be dosed sequentially following the safety and dose-escalation 
assessment of each preceding dose cohort. 
Cohorts 8 and 9: 
For the final 2 dose cohorts (Cohorts 8 and 9), following ticagrelor pretreatment, subjects 
will be randomly assigned (6A:2P) to receive a single IV dose of 9000 or 18000 mg of 
MEDI2452 (PB2452), respectively, or placebo, and will also receive an additional single oral 
dose of 180-mg ticagrelor 24 hours after the initiation of the MEDI2452 (PB2452) or placebo 
infusion. Cohort 8 may be initiated following the safety and dose escalation assessment of 
Cohort 6 (9000-mg MEDI2452 [PB2452]), and Cohort 9 may be initiated following the 
safety and dose escalation assessment of Cohort 7 (18000-mg MEDI2452 [PB2452]). 
Cohort 
Pre-MEDI2452 (PB2452) 
ticagrelor dosing to steady 
state 
(180 mg + 90 mg bid for 
5 doses total) 
MEDI2452 
(PB2452) 
Dose (mg) 
Post-MEDI2452 
(PB2452) 
Ticagrelor (180 mg) 
24 hours following 
MEDI2452 
(PB2452) or placebo 
Number of subjects 
MEDI2452 
(PB2452):placebo 
1 
 
100 
 
3:1 
2 
 
300 
 
3:1 
3 
 
1000 
 
3:1 
4 
180 mg + 90 mg bid 
1000 
 
6:2 
5 
180 mg + 90 mg bid 
3000 
 
6:2 
6 
180 mg + 90 mg bid 
9000 
 
6:2 
7 
180 mg + 90 mg bid 
18000 
 
6:2 
8 
180 mg + 90 mg bid 
9000 
180 mg 
6:2 
9 
180 mg + 90 mg bid 
18000 
180 mg 
6:2 
Abbreviations: BID, twice daily 
Dosing for Cohort 1 (first exposure of MEDI2452 [PB2452] in humans) will proceed with 
two sentinel subjects initially randomly assigned to receive a single IV dose of MEDI2452 
(PB2452) or placebo. Blinded safety data from the sentinel subjects up to 24-hours following 
the MEDI2452 (PB2452) or placebo dose will be reviewed by the investigator before the 
remaining 2 subjects in Cohort 1 are dosed. The remaining subjects will be dosed at least 
24 hours after the sentinel subjects. Additionally, dosing for Cohort 4 (first exposure of the 
combination of MEDI2452 [PB2452] with ticagrelor in humans) will proceed with 2 sentinel 


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subjects pre-treated with ticagrelor prior to receiving a single IV dose of MEDI2452 
(PB2452) or placebo randomized in a 1:1 ratio of active to placebo. Blinded safety data from 
the sentinel subjects up to 24 hours following the ticagrelor and MEDI2452 (PB2452) or 
placebo dose will be reviewed by the investigator before the remaining 6 subjects in Cohort 4 
are dosed. The remaining subjects will be dosed at least 24 hours after the sentinel subjects. 
Subjects in Cohorts 1 through 3 will check in to the clinical site on Day -1. On Day 1, 
subjects will receive a single IV infusion of MEDI2452 (PB2452) or placebo in the morning 
after an overnight fast of approximately 8 hours. Blood samples for PK analysis of 
MEDI2452 (PB2452) in serum will be collected before dosing (within 10 minutes prior to the 
initiation of the MEDI2452 [PB2452] infusion) and through 72 hours after initiation of the 
MEDI2452 (PB2452) infusion. Subjects will undergo end-of-study (EOS) procedures and 
will be discharged from the clinical site on Day 3. Subjects will return for follow-up visits on 
Days 4, 7, and 28 (+2 days). 
Subjects in Cohorts 4 through 9 will check in to the clinical site on Day -3. On Day -2, 
subjects will begin pretreatment with ticagrelor in the morning after an overnight fast of 
approximately 8 hours. On Day 1, subjects will receive a single IV dose of MEDI2452 
(PB2452) or placebo in the morning simultaneous with the 5th ticagrelor dose. Plasma 
samples for PK/PD analysis of MEDI2452 (PB2452), ticagrelor, and its active metabolite 
AR-C124910XX will be collected before dosing (within 10 minutes prior to the initiation of 
the MEDI2452 [PB2452] infusion and 5th ticagrelor dose) and up to 72 hours after initiation 
of the MEDI2452 (PB2452) infusion and the 5th ticagrelor dose. Urine samples for PK 
analysis of ticagrelor and AR-C124910XX will be collected before dosing (within 60 minutes 
prior to the first ticagrelor dose on Day -2) and up to 24 hours after the initiation of the 
MEDI2452 (PB2452) infusion and 5th ticagrelor dose. Subjects in Cohorts 4 through 7 will 
undergo EOS procedures and will be discharged from the clinical site on Day 3 and will 
return for follow-up visits on Days 4, 7, and 28 (+2 days). 
On Day 2, subjects in Cohorts 8 and 9 will receive an additional ticagrelor dose in the 
morning 24 hours following the initiation of the MEDI2452 (PB2452) infusion and 
5th ticagrelor dose. Additional plasma samples for PK/PD analysis of MEDI2452 (PB2452), 
ticagrelor, and AR-C124910XX will be collected through 48 hours after the Day 2 
post-MEDI2452 (PB2452) 6th ticagrelor dose. Subjects in Cohorts 8 and 9 will undergo EOS 
procedures and will be discharged from the clinical site on Day 4 and return for follow-up 
visits on Days 7 and 28 (+2 days). 


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A safety review committee (SRC) will be formed for a blinded review of safety (eg, clinical 
laboratory results, adverse events [AEs], 12-lead electrocardiograms [ECGs], vital signs) and 
available PK data through Day 4 for each dose cohort. The SRC will be minimally composed 
of the on-site investigator, PPD medical monitor, and clinical pharmacologist, and the 
PhaseBio study director and clinical operations lead. Dose escalation to successive cohorts 
will be based upon safety of the preceding cohort. The investigator will make a 
recommendation on whether to proceed to the next predefined dose level, pause dosing for 
review of additional safety and/or PK data, or to adjust the dose of the next dose cohort. The 
decision to adjust or pause the dose or proceed to the next cohort will be made by the SRC. 
The safety data will be reviewed in a blinded manner and must be deemed acceptable to the 
SRC prior to dosing of the next higher dose group. 
Based on the review of safety and PK data, if available, the SRC may choose to repeat a dose 
level, administer a dose less than the previous dose, or escalate to a dose lower than the next 
planned dose. 
Safety and tolerability will be assessed by monitoring and recording of AEs, clinical 
laboratory test results (hematology, coagulation, serum chemistry, and urinalysis), vital sign 
measurements (systolic and diastolic blood pressures, oral body temperature, respiratory rate, 
and heart rate), ECG results, cardiac telemetry monitoring, immunogenicity results, and 
physical examination findings. 
Plasma samples for PK and PD analysis of MEDI2452 (PB2452), ticagrelor, and its active 
metabolite, AR-C124910XX, and urine samples for PK analysis of ticagrelor and 
AR-C124910XX will be collected at specified intervals up to 28 days after dosing. 
The estimated duration of the study for each subject, excluding screening, is approximately 
30 days. 
The overall design of the study is presented in Figure 3–1. 




PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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Women are considered not to be of childbearing potential if they have fulfilled one of the 
following criteria: documentation of irreversible surgical sterilization (ie, hysterectomy, 
or bilateral oophorectomy [not tubal ligation]), or postmenopausal (defined as 
amenorrhea for 12 consecutive months following cessation of all exogenous hormonal 
treatments, and documented plasma follicle-stimulating hormone level >40 IU/mL). Male 
subjects with partners of childbearing potential must agree to use appropriate and 
effective measures of contraception (eg, condom plus diaphragm with spermicide; 
condom plus spermicide) during the study and for 30 days after the last dose of study 
drug, and to refrain from donating sperm for at least 7 days prior to the first dose of study 
drug until at least 90 days following the last dose of study drug. 
5. The subject agrees to comply with all protocol requirements. 
6. The subject is able to provide written informed consent. 
3.2.2 
Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. History of any clinically significant disease or disorder which, in the opinion of the 
investigator, may either put the subject at risk because of participation in the study, or 
influence the results or the subject’s ability to participate in the study. 
2. History or presence of gastrointestinal, hepatic, or renal disease (with the exception of 
Gilbert’s syndrome) or renal insufficiency (ie, estimated glomerular filtration rate 
<60 ml/min/1.73m2), or any other condition known to interfere with absorption, 
distribution, metabolism, or excretion of drugs. 
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks 
of the first administration of study drug. 
4. Any clinically relevant abnormal findings in physical examination, vital signs, 
hematology and coagulation parameters, clinical chemistry, or urinalysis results during 
screening or check-in, which in the opinion of the investigator or medical monitor may 
compromise the safety of the subject in the study or interfere with the evaluation of the 
study drug or reduce the subjects’ ability to participate in the study. Specific exclusionary 
values at screening or check-in blood tests are any of the following: 
• Aspartate transaminase (AST) level >1.5 × upper limit of normal (ULN) 


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• Alanine transaminase (ALT) level >1.5 × ULN 
• Hemoglobin level below the lower limit of normal (hemoglobin levels within 0.5 g/L 
of the lower cut off point may be acceptable based on the judgment of the investigator 
and medical monitor) 
• Thyroid stimulating hormone level above the ULN at screening 
• Prothrombin time or partial thromboplastin time level outside the normal range 
5. The subject has an increased risk of bleeding, including the following: 
• Recent history (within 30 days preceding the first dose of study drug) of 
gastrointestinal bleeding 
• Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding 
• Any recent (within 30 days preceding the first dose of study drug) major trauma 
• History of hemorrhagic disorders that may increase the risk of bleeding (eg, 
hemophilia, von Willebrand’s disease) 
• Inability to discontinue therapy with nonsteroidal anti-inflammatory drugs at 
screening (must discontinue medication within at least 7 days or 5 half-lives, 
whichever is longer, prior to first dose of study drug) 
• Subjects who have taken, within 30 days of screening, any oral or parenteral 
anticoagulant, including low molecular-weight heparin 
• Platelet count < 100,000 mm3 
6. Any clinically important abnormalities in rhythm, conduction, or morphology of the 
resting 12-lead ECG or any abnormalities that may interfere with the interpretation of 
serial ECG changes, including corrected QT interval (QTc) interval changes at screening, 
as judged by the investigator, and also including: 
• Prolonged Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec), 
shortened QTcF <340 msec, or pause >3 seconds at screening, or family history of 
long QT syndrome 


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MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
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• Prolonged PR (PQ) interval >240 msec, intermittent second- or third-degree 
atrioventricular (AV) block or AV dissociation, or shortened PR interval <120 msec at 
screening 
• Incomplete, full, or intermittent bundle branch block (QRS <110 msec with normal 
QRS and T wave morphology is acceptable if there is no evidence of left ventricular 
hypertrophy) 
7. The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus 
antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening. 
8. Abnormal vital signs after 10 minutes supine rest, defined as any of the following: 
• Systolic blood pressure >140 mm Hg 
• Diastolic blood pressure >90 mmHg 
• Heart rate <50 or >100 beats per minute 
Note: Abnormal results may be repeated once for confirmation, at the discretion of the 
investigator 
9. The subject should not participate in the study if they have any ongoing or recent (ie, 
during the screening period) minor medical complaints that may interfere with the 
interpretation of the study data or are considered unlikely to comply with study 
procedures, restrictions, and requirements as judged by the investigator. 
10. History of transient ischemic attack or cardiovascular accident (ischemic or 
hemorrhagic), severe head trauma, intracranial hemorrhage, intracranial neoplasm, 
arteriovenous malformation, aneurysm, or proliferative retinopathy. 
11. The subject is receiving chronic treatment with nonsteroidal anti-inflammatory drugs 
(including aspirin [greater than 100 mg daily]), anticoagulants, or other antiplatelet 
agents that cannot be discontinued (including clopidogrel, prasugrel, ticlopidine, 
dipyridamole, or cilostazol). 
12. The subject is considered to be at risk of bradycardic events (eg, known sick sinus 
syndrome, atrial fibrillation, or second- or third-degree AV block) unless already treated 
with a pacemaker. 


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MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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13. Concomitant oral or IV therapy with strong CYP3A inhibitors, CYP3A substrates with 
narrow therapeutic indices, or strong CYP3A inducers, which cannot be stopped within at 
least 5 half-lives, but not shorter than 10 days, before randomization (a list of examples 
can be found in Section 6.2). 
14. The subject has used any prescription (excluding hormonal birth control) or 
over-the-counter medications (except paracetamol [up to 2 g per day]), including herbal 
or nutritional supplements, within 14 days before the first dose of study drug. 
15. The subject has consumed grapefruit or grapefruit juice, Seville orange or Seville 
orange-containing products (eg, marmalade), or alcohol-, or xanthine-containing products 
within 48 hours before dosing with study drug. 
16. The subject is participating in any other study or is taking part in a non-medication study 
which, in the opinion of the investigator, would interfere with the outcome of the study. 
17. The subject has received another new chemical entity (defined as a compound which has 
not been approved for marketing) or any marketed or investigational biologic agent 
within 30 days of the first administration of study drug in this study. The period of 
exclusion begins 30 days after the final dose or 5 half-lives of the experimental 
medication has elapsed, whichever is longer. 
18. The subject has involvement with any PhaseBio or study site employee or their close 
relatives (eg, spouse, parents, siblings, or children whether biological or legally adopted). 
19. The subject has previously received MEDI2452 (PB2452). 
20. The subject is a smoker or has used nicotine or nicotine-containing products (eg, snuff, 
nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months 
before the first dose of study drug. 
21. The subject has a known or suspected history of drug abuse (including alcohol) as judged 
by the investigator. 
22. The subject has a positive test result for drugs of abuse, alcohol, or cotinine (nicotine 
level above 300 ng/mL) at screening or check-in. 
23. The subject has a planned surgical procedure that will occur during the study (from 
screening through EOS). 


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MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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24. The subject is involved in strenuous activity or contact sports within 24 hours before the 
first dose of study drug and while confined in the clinical site. 
25. The subject has donated blood or plasma within 1 month of screening or any blood 
donation/loss more than 500 mL during the 3 months prior to the first dose of study drug. 
26. The 
subject 
has 
a 
history 
of 
severe 
allergy/hypersensitivity 
or 
ongoing 
allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to 
drugs with a similar chemical structure or class to ticagrelor, any biologic therapeutic 
agent, or any significant food allergy that could preclude a standard diet in the clinical 
site. 
27. Concern for the inability of the subject to comply with study procedures and/or 
follow-up, or, in the opinion of the investigator, the subject is not suitable for entry into 
the study. 
3.2.3 
Subject Restrictions During the Study 
If a subject is unable to comply with any of the following restrictions before study drug 
dosing on Day 1, the subject’s participation in the study will be re-evaluated by the 
investigator in consultation with the sponsor and/or medical monitor on behalf of the sponsor 
and the subject may not be eligible to participate in the study: 
• Subjects in Cohorts 1 through 3 must be willing to remain in the clinic from Day -1 
through 48 hours following MEDI2452 (PB2452) dosing on Day 1. Subjects in Cohorts 4 
through 7 must be willing to remain in the clinic from Day -3 through 48 hours following 
MEDI2452 (PB2452) dosing on Day 1. Subjects in Cohorts 8 and 9 must be willing to 
remain in the clinic from Day -3 through 48 hours following ticagrelor dosing on Day 2. 
• Subjects in Cohorts 1 through 7 must be willing to return to the clinic for follow-up visits 
on Days 4, 7, and 28 (+2 days) and subjects in Cohorts 8 and 9 must be willing to return 
to the clinic for follow-up visits on Days 7 and 28 (+2 days). 
• Subjects must refrain from smoking or use of nicotine or nicotine-containing products as 
specified in Exclusion Criteria #20. 
• Consumption of alcohol is not permitted within 48 hours prior to check-in until discharge 
from the clinical site. 


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MEDI2452 (PB2452) 
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• Subjects must refrain from strenuous exercise for 7 days prior to check-in and for 7 days 
after discharge from the clinical site. Subjects must be willing to maintain their usual 
caloric intake and to consume only food and beverages provided by the clinical site while 
confined at the clinical site. 
3.3 
WITHDRAWAL OF SUBJECTS FROM THE STUDY 
3.3.1 
Reasons for Withdrawal 
Subjects can withdraw consent and discontinue from the study at any time, for any reason, 
without prejudice to further treatment. 
The investigator may withdraw a subject from the study if the subject: 
1. Is non-compliant with the protocol; 
2. Experiences a serious AE (SAE) or intolerable AE(s) that, in the investigator’s opinion, 
requires withdrawal from the study; 
3. Has laboratory safety assessments that reveal clinically significant hematological or 
biochemical changes from baseline values; 
4. Develops symptoms or conditions listed in the exclusion criteria during the course of the 
study and through EOS; 
5. Requires a medication prohibited by the protocol; or 
6. Requests an early discontinuation for any reason. 
The investigator can also withdraw a subject upon the request of the sponsor (PhaseBio 
Pharmaceuticals, Inc) or if the sponsor terminates the study. Upon occurrence of a SAE or 
intolerable AE, the investigator will confer with the sponsor. If a subject is discontinued 
because of an AE, the event will be followed until it is resolved or until stable. 
3.3.2 
Handling of Withdrawals 
Subjects are free to withdraw from the study at any time upon request. Subject participation 
in the study may be stopped at any time at the discretion of the investigator or at the request 
of the sponsor. 
When a subject withdraws from the study, the reason(s) for withdrawal will be recorded by 
the investigator on the relevant page of the electronic case report form (eCRF). Whenever 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 38 
possible, any subject who withdraws from the study prematurely will undergo all EOS 
assessments. Any subject who fails to return for final assessments will be contacted by the 
site in an attempt to have them comply with the protocol. The status of subjects who fail to 
complete final assessments will be documented in the eCRF. 
3.3.3 
Replacements 
At the discretion of the investigator after consultation with the sponsor, any subject who 
withdraws before completing the study, for reasons other than a dose-limiting toxicity (DLT), 
may be replaced. Any replacement subject will be assigned to receive the same treatment as 
the subject he or she is replacing. 
3.4 
STUDY TREATMENTS 
3.4.1 
Method of Assigning Subjects to Treatment Groups 
PPD will generate the randomization schedule. Eligible subjects will be randomly assigned to 
treatment on Day 1 before dosing. Within each cohort, subjects will be randomly assigned to 
receive either MEDI2452 (PB2452) (100, 300, 1000, 3000, 9000, or 18000 mg of MEDI2452 
[PB2452]) or matching placebo in a ratio of 3:1 or 6:2 depending on the cohort. In Cohorts 1 
and 4, 2 subjects will initially receive MEDI2452 (PB2452) or placebo. There will be a safety 
evaluation of at least 24 hours before the remaining subjects in Cohorts 1 and 4 will be dosed 
(Section 3.4.2.1). 
3.4.2 
Treatments Administered 
Subjects will receive one of the following treatments based on the cohort in which they are 
enrolled and the treatment to which they are randomly assigned: 
• Cohort 1: single 30-minute IV infusion of 100 mg MEDI2452 (PB2452) or matching 
placebo in the morning on Day 1 
•  Cohort 2: single 30-minute IV infusion of 300 mg MEDI2452 (PB2452) or matching 
placebo in the morning on Day 1 
• Cohort 3: single 30-minute IV infusion of 1000 mg MEDI2452 (PB2452) or matching 
placebo in the morning on Day 1 
• Cohort 4: single oral dose of 180 mg ticagrelor (2 × 90-mg tablet) in the morning on 
Day -2 followed by 90 mg ticagrelor orally every 12 hours for 4 additional doses; 


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Protocol No. PB2452-PT-CL-0001 
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simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 1000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1 
• Cohort 5: single oral dose of 180 mg ticagrelor (2 × 90-mg tablet) in the morning on 
Day -2 followed by 90 mg ticagrelor orally every 12 hours for 4 additional doses; 
simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 3000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1 
• Cohort 6: single oral dose of 180 mg ticagrelor (2 × 90-mg tablet) in the morning on 
Day -2 followed by 90 mg ticagrelor orally every 12 hours for 4 additional doses; 
simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 9000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1 
• Cohort 7: single oral dose of 180 mg ticagrelor (2 × 90-mg tablet) in the morning on 
Day -2 followed by 90 mg ticagrelor orally every 12 hours for 4 additional doses; 
simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 18000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1 
• Cohort 8: single oral dose of 180 mg ticagrelor (2 × 90-mg tablet) in the morning on 
Day -2 followed by 90 mg ticagrelor orally every 12 hours for 4 additional doses; 
simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 9000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1, followed by a single oral dose of 
180 mg ticagrelor (2 × 90-mg tablet) in the morning on Day 2 (24 hours after initiation of 
the MEDI2452 [PB2452] infusion and 5th ticagrelor dose) 
• Cohort 9: single oral dose of 180 mg ticagrelor (2 × 90-mg tablet) in the morning on 
Day -2 followed by 90 mg ticagrelor orally every 12 hours for 4 additional doses; 
simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 18000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1, followed by a single oral dose of 
180 mg ticagrelor (2 × 90-mg tablet) in the morning on Day 2 (24 hours after initiation of 
the MEDI2452 [PB2452] infusion and 5th ticagrelor dose) 
The assigned study drug (MEDI2452 [PB2452]) or matching placebo will be administered by 
clinical site staff as an IV infusion to subjects in all cohorts in the morning on Day 1 after an 
overnight fast of approximately 8 hours. Study drug will be infused over a 30-minute period. 
Subjects will remain fasted for 2 hours following administration of study drug. 
Treatment with oral ticagrelor will be administered by the clinical site staff to subjects in 
Cohorts 4 through 9 beginning in the morning on Day -2 after an overnight fast of 


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MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
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approximately 8 hours. Subjects will fast for 2 hours prior to receiving the 4 additional doses 
of ticagrelor. For subjects in Cohorts 8 and 9, the 24-hour post-MEDI2452 (PB2452) infusion 
6th ticagrelor dose will be administered by clinical site staff in the morning on Day 2 after an 
overnight fast of approximately 8 hours. All doses of ticagrelor will be administered with 
240 mL of water. 
During fasting periods subjects will restrict their consumption of water to small amounts as 
needed for thirst. At all other times during the study, subjects may consume water ad libitum. 
3.4.2.1 
Dose Escalation 
A SRC will be formed for a blinded review of safety (eg, clinical laboratory results, AEs, 
ECGs, vital signs) and available PK data through Day 4 for each dose cohort. The SRC will 
be minimally composed of the on-site investigator, PPD medical monitor, and clinical 
pharmacologist, and the PhaseBio study director and clinical operations lead. Dose escalation 
to successive cohorts will be based upon safety of the preceding cohort. The investigator will 
make a recommendation on whether to proceed to the next predefined dose level, pause 
dosing for review of additional safety and/or PK data, or to adjust the dose of the next dose 
cohort. The decision to adjust or pause the dose or proceed to the next cohort will be made by 
the SRC. The safety data will be reviewed in a blinded manner and must be deemed 
acceptable to the SRC prior to dosing of the next higher dose group. 
This study is designed such that dose escalation for Cohorts 1 through 7 is allowed only after 
a safety data review of each dose cohort by the SRC. Administration at the next dose level 
will only proceed after the safety data obtained from the previous dose cohort and available 
PK data have been evaluated and approved by the SRC. If the dose level for Cohort 6 is 
determined to be safe and well-tolerated, dosing for Cohort 8 may occur in parallel with 
Cohort 7. 
Based on the review of safety and PK data, if available, the SRC may choose to repeat a dose 
level, administer a dose less than the previous dose, or escalate to a dose lower than the next 
planned dose. In the case of a DLT, SAE, or other significant AE, the SRC may request that 
the study drug assignment be unblinded. 
3.4.2.2 
Infusion or Allergic Reactions 
The administration of study drug must be performed under supervision of trained medical 
staff and where facilities to handle allergic reactions are available. Should a subject 
experience multiple relevant symptoms typical of infusion reactions seen with some 


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recombinant protein drugs (eg, lightheadedness, nausea, chills, fever) (Doesseger et al 2015), 
the study drug infusion may be stopped or slowed at the discretion of the investigator and/or 
the medical monitor. Once symptoms resolve, re-infusion may be attempted. Should a subject 
experience symptoms typical of an allergic reaction (eg, shortness of breath, anaphylaxis, 
urticaria, angioedema), then study drug administration should be discontinued immediately 
and permanently. 
Suspected anaphylaxis should be assessed according to the clinical diagnostic criteria 
outlined by the National Institute of Allergy and Infectious Diseases, which are provided in 
Appendix 6.4. 
For these and other circumstances, subjects will receive appropriate medical treatment at the 
discretion of the investigator. 
3.4.2.3 
 Dose-Limiting Toxicities 
1. A DLT is defined as any AE judged by the investigator to be study drug related (ie, 
causality rated as possible or greater) that is assessed as severe or higher. 
2. A DLT is defined as an SAE or any other medically important AE that impacts subject 
safety experienced by 1 or more subjects in a cohort who, after unblinded safety review, 
are confirmed to have received MEDI2452 (PB2452). Serious AEs that are determined by 
the investigator as related to study drug will be reviewed by the SRC to determine if they 
are DLTs. 
3. A DLT is defined as a clinically significant laboratory abnormality (according to the 
investigator) experienced by 2 or more subjects in a cohort who, after unblinded safety 
review, are confirmed to have received MEDI2452 (PB2452). 
4. A DLT may be considered for a subject who withdraws because of intolerable 
treatment-emergent AE (TEAE). The investigator must use his or her judgment in 
determining whether any event is a DLT. 


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3.4.2.4 
Stopping Criteria 
After completion of Day 4 for each dose cohort, the SRC (see Section 3.4.2.1) will review 
and assess all available safety (eg, clinical laboratory results, AEs, ECGs, vital signs), 
tolerability, and available PK data to make a decision on the dose for next dose cohort. Dose 
escalation may be suspended if any of the following scenarios occur with a reasonable 
possibility of causal relationship with MEDI2452 (PB2452): 
• Events that, in the opinion of the medical monitor and sponsor SRC, contraindicate 
further dosing of additional subjects 
• Any serious AE with a suspected relationship to MEDI2452 (PB2452) in a dose cohort 
• Data from the previous dose cohort indicating safety concerns for the next cohort to be 
dosed at a higher level, such as unanticipated responses (eg, clinically significant changes 
in clinical laboratory data, ECGs, cardiac telemetry, vital signs, or physical examinations) 
• More than 50% of the subjects in a given dose cohort are withdrawn due to poor 
tolerability of MEDI2452 (PB2452) 
• Two or more subjects experiencing severe AEs assessed at least possibly related to 
MEDI2452 (PB2452), or 1 or more subjects experiencing severe AEs assessed at least 
possibly related to MEDI2452 (PB2452) at the discretion of the investigator 
• Two or more subjects have >3 × ULN of either ALT or AST, or > 2 × ULN for bilirubin 
or alkaline phosphatase where no other reason can be found to explain the combination of 
increases 
• Two or more subjects experiencing a severe infusion reaction 
Dose escalation may also be suspended if, in the opinion of the investigator or sponsor, any 
other significant safety or tolerability issues are identified in the comprehensive review of 
available data that warrant further evaluation before additional subjects are dosed. This may 
include emerging nonclinical data, clinically relevant AEs, or relevant data from other 
sources indicating safety concerns even if the event(s) per se does not meet the 
protocol-specified definition of a DLT. 
Dose-limiting toxicities identified during the study will be assessed as potential indicators of 
cumulative toxicity and provide rationale for revision of the maximum tolerated dose (MTD). 
Although this study is not designed to dose to a MTD, the MTD may be reached if 3 or more 


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subjects in a dose cohort experience a DLT as defined in Section 3.4.2.3. No further dosing 
will occur above the MTD. 
3.4.3 
Identity of Investigational Product 
The study drug (MEDI2452 [PB2452]) is supplied as a sterile white to off-white lyophilized 
cake, free from visible foreign particles in a 20R glass vial at a nominal fill volume of 
7.5 mL. MEDI2452 (PB2452) (reconstituted state) is 
 
 
 
The following drug supplies will be used in the study: 
Product 
Supplied as: 
MEDI2452 (PB2452) 
10 gram (g) single dose vial 
Placebo (sterile 0.9% sodium chloride) 
1 liter IV bag 
IV stabilizing solution 
3 mL vial 
Ticagrelor 
90-mg immediate release tablets 
In addition to the study drug, an IV stabilizing solution (IVSS) is supplied to prevent 
adsorption and aggregation of MEDI2452 (PB2452) or placebo to the IV infusion system. 
The IVSS is supplied as a sterile colorless-to-yellow, clear-to-slightly opalescent liquid in a 
3-mL glass vial at a nominal fill of 1 mL. The IVSS vial contains a nominal 1-mL solution of 
 
It should be noted that the lyophilized MEDI2452 (PB2452) study drug must not be 
reconstituted with the IVSS. 
The placebo is a sterile, nonpyrogenic liquid product intended for IV administration. It is 
composed of 0.9% sodium chloride in water for injection, USP. Separate instructions will be 
provided to the clinic for dose dilution, preparation, storage, and administration. 
Ticagrelor 90-mg tablets are supplied as a round, biconvex, yellow, film-coated tablet with a 
“90” above “T” on one side. 
3.4.4 
Management of Clinical Supplies 
3.4.4.1 
Study Drug Packaging and Storage 
PhaseBio Pharmaceuticals, Inc will provide the investigator and clinical site with adequate 
quantities of MEDI2452 (PB2452) and IVSS. Ticagrelor and placebo (0.9% sterile sodium 


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chloride for injection) will be commercially obtained and supplied by PPD and stored in 
accordance with the manufacturer’s label recommendations. 
MEDI2452 (PB2452) will be supplied in a 20R glass vial at a nominal fill volume of 7.5 mL, 
stoppered with siliconized 20 mm chlorobutyl elastomer, Flurotec-coated, single vent 
lyophilization stopper, and sealed with flip-off cap overseal. Following reconstitution with 
water for injection MEDI2452 (PB2452) is further diluted into 0.9% saline for IV infusion. 
The clinical site pharmacy will prepare a single dose for each subject based on the dosing 
cohort and randomization assignment. The concentration will vary between 0.4 mg/mL up to 
72 mg/mL. Separate instructions will be provided to the clinic for dose dilution, preparation, 
storage, and administration. 
The IVSS will be supplied in a 3-mL glass vial at a nominal fill of 1 mL, stoppered with 
siliconized 13-mm chlorobutyl rubber stopper, and sealed with flip-off cap overseal. 
The study drug (MEDI2452 [PB2452]) must be stored in a secure area (eg, a locked, 
temperature-controlled unit), protected from moisture and light, and be stored at 2°C to 8°C 
(36°F to 46°F). The clinical site will be required to keep a temperature log to establish a 
record of compliance with these storage conditions. All study drugs will be kept in a secure 
cabinet or room with access restricted to necessary clinic personnel. 
3.4.4.2 
Study Drug Accountability 
The investigator will maintain accurate records of receipt of all study drugs, including dates 
of receipt. In addition, accurate records will be kept regarding when and how much study 
drug is dispensed and used by each subject in the study. Reasons for departure from the 
expected dispensing regimen must also be recorded. At the completion of the study, to satisfy 
regulatory requirements regarding drug accountability, all study drugs will be reconciled and 
retained or destroyed according to applicable regulations. 
3.4.5 
Blinding 
This is a double-blind study. Neither the subjects nor the investigator will be aware of the 
treatment assignment. Blinding will be maintained throughout the study by use of active and 
placebo dosage forms of similar appearance once prepared. To maintain the blind, only 
designated pharmacy staff at the clinical site will have access to the randomization code and 
will prepare each dose for each subject. In order to prepare preliminary summaries of safety, 
PK, and/or PD data as needed to make timely decisions regarding adjustment of study 
procedures, dosing regimens, or potentially early termination of the study, certain designated 


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staff at PhaseBio who are not part of the study team may be unblinded during the conduct of 
the study (study director, a single biostatistician, and a bioanalytical scientist[s]) before data 
is more generally unblinded. These summaries will not reveal individual subjects’ treatment 
assignments. Except as noted above, all other members of PhaseBio Research and 
Development will remain blinded. Access to the randomization code will be strictly 
controlled according to PPD and PhaseBio standard operating procedures. 
3.4.6 
Breaking the Blind 
A subject may be unblinded in the event of a DLT, SAE, or other event, or if there is a 
medical emergency where the identity of the drug must be known to properly treat a subject. 
A cohort may be unblinded to determine if dose escalation to the next dose level will 
terminate. If a subject becomes seriously ill during the study, the blind will be broken only if 
knowledge of the administered study drug will affect that subject’s treatment options. In the 
event of a medical emergency requiring identification of the study drug administered to an 
individual subject, the investigator will make every attempt to contact the medical monitor to 
explain the need for opening the code within 24 hours of opening the code. The investigator 
will be responsible for documenting the time, date, reason for the code break, and the names 
of the personnel involved. 
A formal unblinded interim analysis (IA) of all accumulated safety, PD, and PK data (as 
needed) will be performed after the last patient in Cohort 6 completes follow-up visit Day 7 
to provide an interim assessment of the safety profile of MEDI2452 (PB2452) after the target 
efficacious dose level has been tested (Cohort 6). Pharmacodynamic and PK data analysis 
will also be included as needed in the IA to provide an assessment of the likely benefit/risk 
profile of the study drug. The prespecified IA analyses will be a subset of the final study 
analyses. The detailed scope of interim analyses will be outlined in a separate document, the 
statistical analysis plan (SAP). An independent statistical group will produce the interim 
analysis. 
3.4.7 
Treatment Compliance 
All doses of study drug will be administered at the clinical site under direct observation of 
clinic personnel and recorded in the eCRF. Clinic personnel will confirm that the subject has 
received the entire dose of study drug. 
The date and time of study drug dosing will be recorded on the appropriate page of the eCRF. 
If a subject does not receive study drug, the reason for the missed dose will be recorded. 


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3.4.8 
Prior and Concomitant Medications 
3.4.8.1 
Prior Medications and Therapies 
Information about prior medications taken by the subject within the 30 days before he or she 
provides informed consent will be recorded in the subject’s eCRF. 
3.4.8.2 
Concomitant Medications and Therapies 
Subjects are prohibited from taking any prescription or over-the-counter medications or 
supplements as described in Section 3.2.2. Paracetamol/acetaminophen may be administered 
at the discretion of the investigator at doses of <2 g/day. 
Subjects are prohibited from therapy with strong CYP3A inhibitors, CYP3A substrates with 
narrow therapeutic indices, or strong CYP3A inducers as described in Section 3.2.2. A list of 
example inhibitors and inducers of CYP3A4 is presented in Section 6.2. 
Subjects are prohibited from taking nonsteroidal anti-inflammatory drugs, anticoagulants, or 
other antiplatelet agents as described in Section 3.2.2. 
Concomitant medications will be coded using the latest version of the World Health 
Organization Drug Dictionary. If drug therapy, with the exception of that specified in the 
protocol, is taken, a joint decision will be made by the investigator and the sponsor to 
continue or discontinue the subject based on the time the medication was administered and its 
pharmacology and pharmacokinetics, and whether the use of the medication will compromise 
the subject safety or interpretation of the data. It is the investigator’s responsibility to ensure 
that details regarding the medication are accurately recorded in the eCRF. 
3.5 
STUDY PROCEDURES 
After signing the informed consent form (ICF) (Section 4.3), subjects will undergo study 
procedures at the time points specified in the schedule of events (Table 6−1). 
3.5.1 
Pharmacokinetic Assessments 
Plasma: 
Blood samples for PK analysis of MEDI2452 (PB2452) in serum will be collected from all 
subjects at the following time points: before dosing (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 
12, 24, 48, and 72 hours, and 7 and 28 days after initiation of the infusion. 


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Plasma samples for determining total concentrations of ticagrelor and its active metabolite 
AR-C124910XX, will be collected from subjects in Cohorts 4 through 9 at the following 
timepoints: before dosing (within 10 minutes prior to the initiation of the MEDI2452 
[PB2452] infusion and 5th ticagrelor dose [Hour 0]), and at 0.5, 1, 2, 3, 6, 12, and 24 hours 
after the initiation of the MEDI2452 (PB2452) infusion and 5th ticagrelor dose. Additional 
samples will be collected from subjects in Cohorts 8 and 9 at the following timepoints: 0.5, 1, 
2, 3, 6, 12, 24, and 48 hours after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. 
Plasma samples for determining unbound concentrations of ticagrelor and AR-C124910XX 
will be collected from subjects in Cohorts 4 through 9 at the following timepoints: before 
dosing (within 10 minutes prior to the initiation of MEDI2452 [PB2452] infusion and 5th 
ticagrelor dose [Hour 0]), and at 0.5, 1, 2, 3, 6, 12, and 24 hours after the initiation of the 
MEDI2452 (PB2452) infusion and 5th ticagrelor dose. Additional samples will be collected 
from subjects in Cohorts 8 and 9 at the following timepoints: 0.5, 1, 2, 3, 6, 12, and 24 hours 
after the Day 2 post-MEDI2452 (PB2452) 6th ticagrelor dose. 
The following plasma PK parameters will be calculated for MEDI2452 (PB2452) using 
actual sampling times rather than scheduled sampling times: 
• Area under the plasma concentration versus time curve (AUC) from time 0 to the time of 
last quantifiable concentration (AUC0-t) 
• Observed maximum plasma concentration (Cmax) 
• Time to reach the observed maximum plasma concentration (Tmax) 
• AUC from time 0 extrapolated to infinity (AUC0-inf) (if data permit) 
• Terminal elimination half-life (t½) (if data permit) 
• Apparent clearance (CL) (if data permit) 
The following plasma PK parameters will be calculated for ticagrelor and AR-C124910XX 
using actual sampling times rather than scheduled sampling times: 
• Cmax 
• Tmax 
• AUC from time 0 to 12 hours after dosing (AUC0-12) 


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• AUC from time 0 to 24 hours after dosing (AUC0-24) 
• AUC0-inf (if data permit) 
• t½ (if data permit) 
The following plasma PK parameters will be calculated for AR-C124910XX using actual 
sampling times rather than scheduled sampling times: 
• Cmax ratio (metabolite:parent) 
• AUC0-24 ratio (metabolite:parent) 
Urine: 
Pooled urine samples to assess urine ticagrelor and AR-C124910XX concentrations will be 
collected from subjects in Cohorts 4 through 9 over the following intervals: before dosing 
(within 60 minutes prior to the first ticagrelor dose on Day -2) and 0 to 6, 6 to 12, and 12 to 
24 hours after the initiation of the MEDI2452 (PB2452) infusion and 5th ticagrelor dose. 
The following PK parameters for ticagrelor and AR-C124910XX concentrations in urine will 
be calculated: 
• Total amount of drug excreted in urine (Ae) 
• Ae from time t1 to t2 hours where the values of t1 to t2 are 0 to 6, 6 to 12, and 12 to 24 
(Aet1-t2) 
• Fraction excreted in urine from 1 to 24 hours after dosing (Fe) 
• Renal clearance (CLr) 
Additional PK parameters may be generated, if needed. 
3.5.1.1 
Pharmacokinetic Sample Collection 
Details on the collection, preparation, and handling of PK blood and urine samples and 
sample shipping instructions will be provided separately to the clinical site in the form of a 
laboratory manual. The clinical site will store all urine and plasma/serum samples at the 
designated temperatures until shipped to the appropriate laboratories for analysis. Back-up 
samples will be maintained by the clinical site under the same conditions, or at a designated 


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storage facility, until PhaseBio Pharmaceuticals indicates that the back-up samples should be 
shipped to the sponsor. 
MEDI2452 (PB2452) and immunogenicity analysis will be performed by: 
PhaseBio Pharmaceuticals, Inc. 
1 Great Valley Parkway, Suite 30 
Malvern, PA 19355 
 
Ticagrelor and AR-C124910XX concentration analysis will be performed by: 
Covance 
1121 East 3900 South, Suite C-110 
Salt Lake City, UT 84124 
 
3.5.1.2 
Bioanalytical Methods 
Pharmacokinetic samples for total and free ticagrelor and AR-C124910XX will be analyzed 
using a validated liquid chromatography coupled with tandem mass spectrometry assay in 
human plasma. Pharmacokinetic samples for MEDI2452 (PB2452) will be analyzed using an 
immunoassay. The methods will be validated as per International Council for Harmonisation 
(ICH) standards and fit for purpose. Details of the bioanalytical methods and validation will 
be available in a separate bioanalytical report. 
3.5.2 
Pharmacodynamic Assessments 
Blood samples for PD analysis will be collected from subjects in Cohorts 4 through 9 at the 
following time points: before dosing (within 60 minutes prior to first ticagrelor dose on 
Day -2) and again before dosing (within 10 minutes prior to the initiation of the MEDI2452 
[PB2452] infusion and 5th ticagrelor dose [Hour 0]) and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours 
after the initiation of the MEDI2452 (PB2452) infusion and 5th ticagrelor dose. Additional 
blood samples for PD analysis from subjects in Cohorts 8 and 9 will be collected at the 
following time points: 1, 2, 6, and 12 hours after the Day 2 post-MEDI2452 (PB2452) 6th 
ticagrelor dose. Subjects will be scheduled to provide adequate time for performance of PD 
sample handling and processing within the stated guidelines outlined in Section 3.5.2.1. 


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The following PD parameters will be calculated using the data generated by LTA, P2Y12 
reaction units (PRU), and platelet reactivity index (PRI) assays: 
LTA: 
• inhibition of platelet aggregation (IPA) (max and final extent) induced by 20µM 
adenosine diphosphate (ADP) at each assessment point 
• inhibition of maximal platelet aggregation (IPAmax) 
• time to IPAmax (TIPAmax) 
VerifyNow™P2Y12: 
• PRU at each assessment point 
VASP by ELISA: 
• PRI at each assessment point 
Additional PD parameters may be generated, if needed. 
3.5.2.1 
Pharmacodynamic Sample Collection 
Blood samples will be collected in blood collection tubes specific for each of the 3 assays: 
• LTA: 3.2% sodium citrate (blue-top) (2 tubes, 4.5 mL blood each) 
• VerifyNow™P2Y12: Greiner Bio-One Vacuette® partial fill blood collection tube 
containing 3.2% sodium citrate (approximately 3 mL blood) 
• VASP: 3.2% sodium citrate (blue-top) (1.8 mL blood) 
The LTA assays must be completed within 3 hours of venipuncture and the VerifyNow test 
must be completed within 4 hours of venipuncture. Results from these assays will be 
forwarded to CirQuest Labs for ongoing evaluation of testing and data adjudication. The PRI 
assay must be completed within 48 hours of venipuncture and will be shipped overnight to 
CirQuest Labs, LLC at 140 Collins Avenue, Memphis, TN 38112
 
Instructions for sample collection, preparation, and shipping will be provided separately to 
the clinical site. 


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3.5.2.2 
Bioanalytical Methods 
Details of the bioanalytical methods and validation will be available in a separate 
bioanalytical report. 
3.5.3 
Safety Assessments 
Safety and tolerability will be assessed by monitoring and recording of AEs, clinical 
laboratory test results (hematology, coagulation, serum chemistry, and urinalysis), vital sign 
measurements (systolic and diastolic blood pressures, oral body temperature, respiratory rate, 
and heart rate), 12-lead ECG results, cardiac telemetry, and physical examination findings. 
3.5.4 
Adverse Events 
3.5.4.1 
Adverse Event Definitions 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to study drug or their clinical significance. If there is 
any doubt as to whether a clinical observation is an AE, the event should be reported. 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug-related. Subjects will be instructed to contact the 
investigator at any time after randomization if any symptoms develop. 
A TEAE is defined as any event not present before exposure to study drug (MEDI2452 
[PB2452]) or any event already present that worsens in intensity or frequency after exposure. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
study drug caused the AE. For the purposes of investigational new drug safety reporting, 
“reasonable possibility” means that there is evidence to suggest a causal relationship between 
the study drug and the AE. A suspected adverse reaction implies a lesser degree of certainty 
about causality than adverse reaction, which means any AE caused by a study drug. 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions for which there are reasons to conclude that the drug caused the 
event. 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
investigator brochure or at the specificity or severity that has been observed with the study 
drug being tested; or, if an investigator brochure is not required or available, is not consistent 
with the risk information described in the general investigational plan or elsewhere in the 


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current application. For example, under this definition, hepatic necrosis would be unexpected 
(by virtue of greater severity) if the investigator brochure referred only to elevated hepatic 
enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be 
unexpected (by virtue of greater specificity) if the investigator brochure listed only cerebral 
vascular accidents. “Unexpected,” as used in this definition, also refers to AEs or suspected 
adverse reactions that are mentioned in the investigator brochure as occurring with a class of 
drugs or as anticipated from the pharmacological properties of the drug, but are not 
specifically mentioned as occurring with the particular drug under investigation. 
An AE or suspected adverse reaction is considered an SAE/suspected unexpected serious 
adverse reaction if, in the view of either the investigator or sponsor, it results in any of the 
following outcomes: 
• Death 
• Life-threatening AE 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly or birth defect 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
An AE or suspected adverse reaction is considered “life threatening” if, in the view of either 
the investigator or sponsor, its occurrence places the subject at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe 
form, might have caused death. 


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Special attention will be given to DLTs and the MTD, if applicable. Dose-limiting toxicity is 
defined in Section 3.4.2.3. Dose escalation to the next dose level is described in 
Section 3.4.2.1. 
The overall safety profile, including but not limited to DLT and MTD will be used in the 
selection of the starting dose(s) in future studies of MEDI2452 (PB2452) administered by 
infusion. 
3.5.4.2 
Eliciting and Documenting Adverse Events 
The investigator is responsible for ensuring that all AEs and SAEs are recorded in the eCRF 
and reported to PhaseBio Pharmaceuticals, Inc. Adverse events will be assessed from the 
time of pretreatment dosing with ticagrelor on Day -2 until completion of all study 
procedures and EOS assessments (Day 28). 
Subjects may spontaneously report and/or will be asked a standard question to elicit any 
medically related changes in their well-being. They will also be asked if they have used any 
new medications, or changed concomitant medication regimens (both prescription and 
over-the-counter medications). 
In addition to subject observations, AEs will be documented from any data collected on the 
AE page of the eCRF (eg, laboratory values, physical examination findings, and ECG 
changes) or other documents that are relevant to subject safety. 
3.5.4.3 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page of the eCRF. 
Information to be collected includes drug treatment, type of event, time of onset, dosage, 
investigator-specified assessment of severity and relationship to study drug, time of 
resolution of the event, seriousness, as well as any required treatment or evaluations, and 
outcome. The AEs resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed until they are resolved or stable or judged by the investigator to be 
not clinically significant. The Medical Dictionary of Regulatory Activities will be used to 
code all AEs. 
Any medical condition that is present at the time that the subject is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time during the 
study, it should be recorded as an AE. 


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Any AE considered serious by the investigator or which meets SAE criteria (Section 3.5.4.1) 
must be reported to the sponsor immediately (after the investigator has confirmed the 
occurrence of the SAE). The investigator will assess whether there is a reasonable possibility 
that the study drug caused the SAE. The sponsor will be responsible for notifying the 
relevant regulatory authorities of any SAE as outlined in the US Title 21 Code of Federal 
Regulations (CFR) Parts 312 and 320. The investigator is responsible for notifying the 
institutional review board (IRB) directly. 
The following contact information is to be used for SAE reporting: 
PPD Medical Monitor: 
Rahul Bhatnagar, MD 
PPD 
7551 Metro Center Drive, Suite 300 
Austin, TX 78744 
 
 
 
3.5.4.4 
Assessment of Severity 
The severity (or intensity) of an AE refers to the extent to which it affects the subject’s daily 
activities and will be classified as mild, moderate, or severe using the following criteria: 
• Mild: These events require minimal or no treatment and do not interfere with the 
subject’s daily activities. 
• Moderate: These events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with normal 
functioning. 
• Severe: These events interrupt a subject’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. An AE characterized as 
intermittent requires documentation of onset and duration of each episode. 


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3.5.4.5 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to study drug is part of the 
documentation process but is not a factor in determining what is or is not reported in the 
study. 
The investigator will assess causality (ie, whether there is a reasonable possibility that the 
study drug caused the event) for all AEs and SAEs. The relationship will be characterized 
using the following classification: 
• Unrelated: This relationship suggests that there is no association between the study drug 
and the reported event. 
• Possible: This relationship is based on evidence suggesting a causal relationship between 
the study drug and the AE, ie, there is a reasonable possibility that the drug caused the 
event. The event follows a reasonable temporal sequence from the time of drug 
administration or follows a known response pattern to the study drug, but could also have 
been produced by other factors. 
• Probable: This relationship suggests that a reasonable temporal sequence of the event 
with drug administration exists and, based upon the known pharmacological action of the 
drug, known or previously reported adverse reactions to the drug or class of drugs, or 
judgment based on the investigator’s clinical experience, the association of the event with 
the study drug seems likely. 
• Definite: This relationship suggests that a definite causal relationship exists between drug 
administration 
and 
the 
AE, 
and 
other 
conditions 
(concurrent 
illness, 
progression/expression of disease state, or concurrent medication reaction) do not appear 
to explain the event. 
3.5.4.6 
Follow-up of Adverse Events 
All AEs must be reported in detail on the appropriate page of the eCRF and followed until it 
is resolved or stable or judged by the investigator to be not clinically significant. 
3.5.5 
Clinical Laboratory Testing 
Clinical laboratory tests will be performed by PPD Central Laboratory. Blood will be 
collected at the time points indicated in the schedule of events (Table 6−1) and will be 
prepared using standard procedures. Repeat clinical laboratory tests may be performed at the 


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discretion of the investigator, if necessary, to evaluate inclusion and exclusion criteria or 
clinical laboratory abnormalities. The clinical laboratory that will perform the tests will 
provide the reference ranges for all clinical laboratory parameters. 
The following clinical laboratory assessments will be performed: 
Hematology 
Hematocrit, hemoglobin, mean corpuscular hemoglobin, mean 
corpuscular hemoglobin concentration, mean corpuscular volume, 
platelet count, red blood cell count, and total and differential leukocyte 
count 
Coagulation 
 
Activated partial thromboplastin time, international normalized ratio, 
partial thromboplastin time, and prothrombin time 
Serum Chemistry 
Alanine aminotransferase, albumin, alkaline phosphatase, aspartate 
aminotransferase, bicarbonate, bilirubin (total and direct), blood urea 
nitrogen, calcium, carbon dioxide, chloride, cholesterol (total, 
high-density lipoprotein, and calculated low-density lipoprotein), 
creatine 
phosphokinase, 
creatinine, 
gamma-glutamyltransferase, 
globulin, glucose, lactate dehydrogenase, magnesium, phosphorus, 
potassium, sodium, thyroid stimulating hormone (screening only) total 
protein, triglycerides, and uric acid 
Urinalysis 
Appearance, bilirubin, color, glucose, ketones, leukocyte esterase, 
reflex microscopy (performed if dipstick is positive for protein or 
blood value of 1+ or greater; and includes bacteria, casts, crystals, 
epithelial cells, red blood cells, and white blood cells), nitrites, occult 
blood, pH, protein, specific gravity, turbidity, and urobilinogen 
Serology 
Hepatitis B surface antigen, hepatitis C virus antibody, and human 
immunodeficiency virus types 1 and 2 antibodies (screening only) 
Other analyses 
Urine drug screen (amphetamines, barbiturates, benzodiazepines, 
cannabinoids, cocaine, cotinine, methylenedioxymethamphetamine 
[MDMA], 
opiates, 
phencyclidine, 
propoxyphene, 
and 
tetrahydrocannabinol) (screening and check-in only) 
Urine Alcohol (check-in only) 
Female subjects: Follicle-stimulating hormone, serum pregnancy test 
(human chorionic gonadotropin [at screening, check-in, and Day 28 
only]) 
Immunogenicity 
Anti-drug antibodies (ADA) 
When procedures are overlapping and occurring at the same time point, the order of priority 
for procedures should be PK blood collection, 12-lead ECG, vital sign measurements, and 
then clinical laboratory tests. 


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Abnormal clinical laboratory values will be flagged as either high or low (or normal or 
abnormal) based on the reference ranges for each laboratory parameter. The investigator will 
determine whether any of the abnormally high or low results are clinically significant or not 
clinically significant. Clinical significance is defined as any variation in results that has 
medical relevance and may result in an alteration in medical care (eg, active observation, 
diagnostic measures, or therapeutic measures). If a clinically significant change from the 
screening value is noted, the clinically significant value and reason for clinical significance 
will be documented on the AE page of the eCRF. The investigator will continue to monitor 
the subject with additional assessments until the values have reached the reference range or 
the values at screening or until the investigator determines that follow-up is no longer 
medically necessary. 
3.5.6 
Vital Sign Measurements 
Vital signs will be measured at the time points indicated in the schedule of events 
(Table 6−1). Vital sign measurements will include systolic and diastolic blood pressures, oral 
body temperature, respiratory rate, and heart rate. The subject will be seated for at least 
10 minutes before all measurements are taken. 
The investigator will determine whether any of the vital sign measurements are clinically 
significant or not clinically significant. Clinical significance is defined as any variation in 
results that has medical relevance and may result in an alteration in medical care (eg, active 
observation, diagnostic measures, or therapeutic measures). If a clinically significant change 
from the screening values is noted, the clinically significant value and reason for clinical 
significance will be documented on the AE page of the subject’s eCRF. The investigator will 
continue to monitor the subject with additional assessments until the value has reached the 
reference range or the value at screening or until the investigator determines that follow-up is 
no longer medically necessary. 
3.5.7 
Twelve-Lead Electrocardiogram 
Triplicate 12-lead ECGs will be obtained after the subject has been in the supine position for 
at least 10 minutes at the time points indicated in the schedule of events (Table 6−1) and as 
indicated by AEs or telemetry findings. The investigator should review and sign the ECG for 
any immediate issues. Electrocardiogram assessments will include comments on whether the 
tracings are normal or abnormal, rhythm, presence of arrhythmia or conduction defects, 
morphology, any evidence of myocardial infarction, or ST-segment, T-Wave, and U-Wave 
abnormalities. In addition, measurements of the following intervals will be measured and 
reported: RR interval, PR interval, QRS width, and QTcF. 


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The investigator will determine whether any of the 12-lead ECG results are clinically 
significant or not clinically significant. Clinical significance is defined as any variation in 
results that has medical relevance and may result in an alteration in medical care (eg, active 
observation, diagnostic measures, or therapeutic measures). If a clinically significant change 
from screening is noted, the clinically significant value and reason for clinical significance 
will be documented on the AE page of the subject’s eCRF. The investigator will continue to 
monitor the subject with additional assessments until either the values have reached reference 
range or the values at screening or until the investigator determines that follow-up is no 
longer medically necessary. 
3.5.8 
Physical Examinations 
A standard physical examination will be performed at the time points indicated in the 
schedule of events (Table 6−1). The examination will include assessment of skin, head, ears, 
eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, and 
musculoskeletal system/extremities. A brief physical examination will include assessment of 
skin (including any signs for cutaneous erythema), lungs, cardiovascular system, and 
abdomen (liver, spleen). 
Interim physical examinations will be performed at the discretion of the investigator, if 
necessary, to evaluate AEs or clinical laboratory abnormalities. 
Height and weight will be measured and body mass index will be calculated at screening 
only. 
3.5.9 
Infusion Site Assessments 
The infusion site will be examined by the investigator or designee periodically for pain, 
tenderness, erythema/redness, and induration/swelling as indicated in the schedule of events 
(Table 6−1). Any infusion site reactions observed will be monitored and recorded as AEs. 
See Appendix 6.3 for infusion site assessment scales. 
3.5.10 
Telemetry Monitoring 
Cardiac telemetry will be performed at the time points indicated in the schedule of events 
(Table 6−1) to monitor heart rate and rhythm activity as real-time safety measurements. The 
clinical research site will be responsible for providing trained study personnel for monitoring 
of telemetry. The telemetry monitoring system utilized will be maintained in accordance with 
the clinical research site’s standard operating procedures. 


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The investigator will determine if any of the telemetry findings are clinically significant. 
Clinical significance is defined as any variation in results that has medical relevance and may 
result in an alteration in medical care (eg, active observation, diagnostic measures, or 
therapeutic measures). 
If a clinically significant change from the telemetry findings on Day -1 (approximately 
12 hours before the start of infusion) is noted, the clinically significant value and reason for 
clinical significance will be documented in the AE page of the subject’s eCRF. Clinically 
significant abnormalities should be followed up by performing a 12-lead ECG. The 
investigator will continue to monitor the subject with additional assessments until the 
investigator determines that follow-up is no longer medically necessary. 
3.5.11 
Immunogenicity 
Immunogenicity (antibody) samples will be screened for the presence of binding ADA at the 
time points indicated in the schedule of events (Table 6−1). 
3.6 
STATISTICAL ANALYSIS PLAN 
3.6.1 
Sample Size Calculations 
The sample size (N = 60) for this study is based on clinical and practical considerations and 
not on a formal statistical power calculation. The sample size is considered sufficient to 
adequately assess the safety, PK, and PD profiles of MEDI2452 (PB2452) and the PK and 
PD profiles of ticagrelor. 
3.6.2 
Analysis Populations 
The Safety population will include all subjects who receive any amount of study drug. 
The PK population will include subjects who receive at least 1 dose of study drug and have at 
least 1 measurable PK concentration. 
The PD population will include subjects who receive at least 1 dose of ticagrelor and have at 
least 1 measurable post dose LTA value. 
3.6.3 
Statistical Analysis 
Details of all statistical analyses will be described in a separate SAP. All data collected will 
be presented in data listings. Data from subjects excluded from an analysis population will be 
presented in the data listings but not included in the calculation of summary statistics. 


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Data from subjects receiving placebo will be pooled across cohorts for all presentations. 
For categorical variables, frequencies and percentages will be presented. Continuous 
variables will be summarized using descriptive statistics (number of subjects, mean, median, 
SD, minimum, and maximum). 
Demographic and baseline characteristics will be summarized. The number of subjects who 
enroll in the study and the number and percentage of subjects who complete the study will be 
presented. Frequency and percentage of subjects who withdraw or discontinue from the 
study, and the reason for withdrawal or discontinuation, will also be summarized. 
3.6.3.1 
Safety Analyses 
Adverse events will be coded by preferred term and system organ class using the latest 
version of the Medical Dictionary for Regulatory Activities. All AE data will be presented in 
a data listing. Treatment-emergent AEs will be summarized by treatment and overall, as well 
as by severity and relationship to study drug. Serious AEs and AEs leading to discontinuation 
of study drug will be presented in the data listings. 
Actual values and changes from baseline for clinical laboratory test results, vital sign 
measurements, and 12-lead ECG results will be summarized by treatment at each time point 
using descriptive statistics (number of subjects, mean, SD, median, minimum, and 
maximum). Shift tables will be generated for clinical laboratory test results. Clinical 
laboratory test results, vital sign measurements, 12-lead ECG results, and physical 
examination findings will be presented in data listings. 
3.6.3.2 
Pharmacokinetic Analyses 
Plasma concentration data will be listed and summarized by time point for each dose level 
using descriptive statistics (number of subjects, mean, SD, coefficient of variation [CV], 
median, minimum, and maximum). Plasma concentration versus time profiles for each 
subject will be presented graphically. The mean plasma concentrations versus scheduled time 
profiles will be presented graphically by dose. 
The PK parameters of MEDI2452 (PB2452), ticagrelor, and AR-C124910XX will be 
determined using noncompartmental methods using Phoenix® WinNonlin® (Certara, L.P., 
Princeton, NJ) Version 6.4 or higher or SAS® Version 9.3 or higher (SAS Institute Inc., Cary, 
NC). Pharmacokinetic parameters will be summarized for each dose level using descriptive 
statistics (number of subjects, mean, SD, CV, median, minimum, and maximum). Geometric 
means will be reported for AUCs and Cmax. Actual sampling times, rather than scheduled 


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sampling times, will be used in all calculations of PK parameters. However, for ease of 
presentation, scheduled sampling times will be used to present results in tables, listings, and 
figures. 
Dose proportionality will be tested using the power regression model for AUC0-inf, AUC0-t, 
and Cmax of MEDI2452 (PB2452) in Cohorts 4, 5, 6, and 7. 
3.6.3.3 
Pharmacodynamic Analyses 
Pharmacodynamic data will be summarized for each time point using descriptive statistics 
(number of subjects, mean, SD, CV, median, minimum, and maximum). Pharmacodynamic 
parameters will also be summarized for each dose level. 
3.6.4 
Handling of Missing Data 
Concentrations that are below the limit of quantification (BLQ) will be treated as zero for 
descriptive statistics. Mean BLQ concentrations will be presented as BLQ, and the SD and 
CV will be reported as not applicable. Missing concentrations will be excluded from the 
calculations. 
For the PK analysis, BLQ values will be treated as zero with the exception that a BLQ value 
between 2 quantifiable concentrations will be set as missing. Missing concentrations will be 
treated as missing from the PK parameter calculations. If consecutive BLQ concentrations 
are followed by quantifiable concentrations in the terminal phase, those concentrations after 
BLQ concentrations will be treated as missing. 
3.6.5 
Interim Analyses 
A formal unblinded IA of all accumulated safety, PD, and PK data (as needed) will be 
performed after the last patient in Cohort 6 completes follow-up visit Day 7 to provide an 
interim assessment of the safety profile of MEDI2452 (PB2452) after the target efficacious 
dose level has been tested (Cohort 6). Pharmacodynamic and PK data analysis will also be 
included as needed in the interim analysis to provide an assessment of the likely benefit/risk 
profile of the study drug. The prespecified IA analyses will be a subset of the final study 
analyses. The detailed scope of IA will be outlined in a separate document, the SAP. An 
independent statistical group will produce the interim analysis. 
Separate from the IA, blinded safety data review for each dose cohort will be performed 
before dosing in the next cohort is allowed (Section 3.4.2.1). 


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Interim noncompartmental analyses of PK data and PK/PD modeling will be performed as 
needed. 
3.7 
DATA QUALITY ASSURANCE 
This study will be conducted using quality processes described in applicable procedural 
documents. The quality management approach to be implemented will be documented and 
will comply with the current ICH guidance on quality and risk management. All aspects of 
the study will be monitored for compliance with applicable government regulatory 
requirements, current Good Clinical Practice, the protocol, and standard operating 
procedures. The monitor will maintain current personal knowledge of the study through 
observation, review of study records and source documentation, and discussion of the 
conduct of the study with the investigator and staff. Electronic CRFs and electronic data 
capture will be utilized. The electronic data capture system is validated and compliant with 
US Title 21 CFR Part 11. Each person involved with the study will have an individual 
identification code and password that allows for record traceability. There may be an internal 
quality review audit of the data and additional reviews by the clinical monitor. 


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4. 
INVESTIGATOR OBLIGATIONS 
The following administrative items are meant to guide the investigator in the conduct of the 
study and may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Changes will be reported to the IRB 
but will not result in protocol amendments. 
4.1 
CONFIDENTIALITY 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the subject (or the subject’s legal guardian), except as necessary for monitoring 
and auditing by the sponsor, its designee, the US Food and Drug Administration (FDA), or 
the IRB. 
The investigator and all employees and coworkers involved with this study may not disclose 
or use for any purpose other than performance of the study, any data, record, or other 
unpublished, confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
4.2 
INSTITUTIONAL REVIEW 
Federal regulations and the ICH guidelines require that approval be obtained from an IRB 
before participation of human subjects in research studies. Before study onset, the protocol, 
ICF, advertisements to be used for the recruitment of study subjects, and any other written 
information regarding this study to be provided to the subject or the subject’s legal guardian 
must be approved by the IRB. Documentation of all IRB approvals and of the IRB 
compliance with the ICH harmonised tripartite guideline E6(R2): Good Clinical Practice will 
be maintained by the site and will be available for review by the sponsor or its designee. 
All IRB approvals should be signed by the IRB chairman or designee and must identify the 
IRB name and address, the clinical protocol by title or protocol number or both and the date 
approval or a favorable opinion was granted. 
4.3 
SUBJECT CONSENT 
Written informed consent in compliance with US Title 21 CFR Part 50 shall be obtained from 
each subject before he or she enters the study or before performing any unusual or nonroutine 


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procedure that involves risk to the subject. If any institution-specific modifications to 
study-related procedures are proposed or made by the site, the consent should be reviewed by 
the sponsor or its designee or both before IRB submission. Once reviewed, the investigator 
will submit the ICF to the IRB for review and approval before the start of the study. If the 
ICF is revised during the course of the study, all active participating subjects must sign the 
revised form. 
Before recruitment and enrollment, each prospective subject or his/her legal guardian will be 
given a full explanation of the study and be allowed to read the approved ICF. Once the 
investigator is assured that the subject/legal guardian understands the implications of 
participating in the study, the subject/legal guardian will be asked to give his or her consent 
to participate in the study by signing the ICF. A copy of the ICF will be provided to the 
subject/legal guardian. 
4.4 
STUDY REPORTING REQUIREMENTS 
By participating in this study the investigator agrees to submit reports of SAEs according to 
the time line and method outlined in this protocol. In addition, the investigator agrees to 
submit annual reports to his or her IRB as appropriate. 
4.5 
FINANCIAL DISCLOSURE AND OBLIGATIONS 
The investigator is required to provide financial disclosure information to allow the sponsor 
to submit the complete and accurate certification or disclosure statements required under US 
Title 21 CFR Part 54. In addition, the investigator must provide to the sponsor a commitment 
to promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
Neither the sponsor nor PPD is financially responsible for further testing or treatment of any 
medical condition that may be detected during the screening process. In addition, in the 
absence of specific arrangements, neither the sponsor nor PPD is financially responsible for 
further treatment of the disease under study. 
4.6 
INVESTIGATOR DOCUMENTATION 
Prior to beginning the study, the investigator will be asked to comply with ICH 
E6(R2) Section 8.2 and US Title 21 of the CFR by providing the following essential 
documents, including but not limited to: 
• IRB approval, 


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• An original investigator-signed investigator agreement page of the protocol, 
• Form FDA 1572, fully executed, and all updates on a new fully executed Form FDA 
1572, 
• Curriculum vitae for the principal investigator and each subinvestigator listed on Form 
FDA 1572. Current licensure must be noted on the curriculum vitae. Curriculum vitae 
will be signed and dated by the principal investigators and subinvestigators at study 
start-up, indicating that they are accurate and current. 
• Financial disclosure information to allow the sponsor to submit complete and accurate 
certification or disclosure statements required under US Title 21 CFR Part 54. In 
addition, the investigators must provide to the sponsor a commitment to promptly update 
this information if any relevant changes occur during the course of the investigation and 
for 1 year after the completion of the study. 
• An IRB-approved ICF, samples of site advertisements for recruitment for this study, and 
any other written information about this study that is to be provided to the subject or legal 
guardians, and 
• Laboratory certifications and reference ranges for any local laboratories used by the site, 
in accordance with US Title 42 CFR Part 493. 
4.7 
STUDY CONDUCT 
The investigator agrees to perform all aspects of this study in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, ICH E6(R2): Good Clinical 
Practice, the protocol, and all national, state, and local laws or regulations. 
4.8 
DATA COLLECTION 
4.8.1 
Case Report Forms and Source Documents 
Site personnel will maintain source documentation and enter subject data into the eCRF as 
accurately as possible and will rapidly respond to any reported discrepancies. 
Electronic CRFs and electronic data capture will be utilized. The electronic data capture 
system is validated and compliant with US Title 21 CFR Part 11. Each person involved with 
the study will have an individual identification code and password that allows for record 
traceability. Thus, the system, and subsequently any investigative reviews, can identify 


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coordinators, investigators, and individuals who have entered or modified records, as well as 
the time and date of any modifications. There may be an internal quality review audit of the 
data and additional reviews by the clinical monitor. 
Each eCRF is presented as an electronic copy, allowing data entry by site personnel, who can 
add and edit data, add new subjects, identify and resolve discrepancies, and view records. 
This system provides immediate direct data transfer to the database, as well as immediate 
detection of discrepancies, enabling site coordinators to resolve and manage discrepancies in 
a timely manner. 
Paper copies of the eCRFs and other database reports may be printed and signed by the 
investigator. This system provides site personnel, monitors, and reviewers with access to 
hardcopy audits, discrepancy reviews, and investigator comment information. 
4.9 
ADHERENCE TO PROTOCOL 
The investigator agrees to conduct the study as outlined in this protocol, in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 
4.10 
REPORTING ADVERSE EVENTS 
By participating in this study, the investigator agrees to submit reports of SAEs according to 
the timeline and method outlined in this protocol. In addition, the investigator agrees to 
submit annual reports to his or her IRB as appropriate. The investigator also agrees to 
provide the sponsor with an adequate report, if applicable, shortly after completion of the 
investigator’s participation in the study. 
4.11 
INVESTIGATOR’S FINAL REPORT 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB with a summary of the study’s 
outcome, and the sponsor and regulatory authority(ies) with any reports required. 
4.12 
RECORDS RETENTION 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study drug. These documents should be 
retained for a longer period, however, if required by the applicable regulatory requirements 


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or by an agreement with the sponsor. It is the sponsor’s responsibility to inform the 
investigator/institution as to when these documents no longer need to be retained. 
4.13 
PUBLICATIONS 
After completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the sponsor will be 
responsible for these activities and will work with the investigators to determine how the 
manuscript is written and edited, the number and order of authors, the publication to which it 
will be submitted, and any other related issues. The sponsor has final approval authority over 
all such issues. 
Data are the property of the sponsor and cannot be published without their prior 
authorization, but data and any publication thereof will not be unduly withheld. 


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5. 
STUDY MANAGEMENT 
5.1 
MONITORING 
5.1.1 
Monitoring of the Study 
The clinical monitor, as a representative of the sponsor, is obligated to follow the study 
closely. In doing so, the monitor will visit the investigator and study site at periodic intervals 
in addition to maintaining necessary telephone and email contact. The monitor will maintain 
current personal knowledge of the study through observation, review of study records and 
source documentation, and discussion of the conduct of the study with the investigator and 
staff. 
All aspects of the study will be carefully monitored by the sponsor or its designee for 
compliance with applicable government regulation with respect to current ICH E6(R2) 
guidelines and standard operating procedures. 
5.1.2 
Inspection of Records 
The investigator and institution involved in the study will permit study-related monitoring, 
audits, IRB review, and regulatory inspections by providing direct access to all study records. 
In the event of an audit, the investigator agrees to allow the sponsor, their representatives, the 
FDA, or other regulatory agency access to all study records. 
The investigator should promptly notify the sponsor and study site(s) of any audits scheduled 
by any regulatory authorities and promptly forward copies of any audit reports received to 
the sponsor. 
5.2 
MANAGEMENT OF PROTOCOL AMENDMENTS AND 
DEVIATIONS 
5.2.1 
Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent, 
immediate hazard to the subject, must be reviewed and approved by the sponsor or designee. 
Amendments to the protocol must be submitted in writing to the investigator’s IRB for 
approval before subjects are enrolled into an amended protocol. 
5.2.2 
Protocol Deviations 
The investigator or designee must document and explain in the subject’s source 
documentation any deviation from the approved protocol. The investigator may implement a 


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deviation from, or a change to, the protocol to eliminate an immediate hazard to study 
subjects without prior IRB approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 
should be submitted to the IRB for review and approval, to the sponsor for agreement, and to 
the regulatory authorities, if required. 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures defined in the protocol. An important protocol deviation (sometimes referred to as a 
protocol violation or a major protocol deviation) is a subset of protocol deviations that might 
significantly affect the reliability of the study data or that might significantly affect a subject's 
safety. An important deviation can include nonadherence to inclusion or exclusion criteria or 
nonadherence to FDA regulations or ICH E6(R2) guidelines. 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. The investigator will be notified in writing by the monitor of deviations. 
The IRB should be notified of protocol deviations, if appropriate, in a timely manner. 
5.3 
STUDY TERMINATION 
Although the sponsor has every intention of completing the study, they reserve the right to 
discontinue it at any time for clinical or administrative reasons. 
The end of the study is defined as the date on which the last subject completes the last visit 
(includes the EOS visit and any additional long-term follow-up). Any additional long-term 
follow-up that is required for monitoring of the resolution of an AE or finding may be 
appended to the clinical study report. 
5.4 
FINAL REPORT 
Whether the study is completed or prematurely terminated, the sponsor will ensure that 
clinical study reports are prepared and provided to the regulatory agency(ies) as required by 
the applicable regulatory requirement(s). The sponsor will also ensure that clinical study 
reports in marketing applications meet the standards of the ICH harmonised tripartite 
guideline E3: Structure and content of clinical study reports. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and have the opportunity 
to review complete study results. 


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Upon completion of the clinical study report, the investigator(s) will be provided with the 
final approved clinical study report, as appropriate. 


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6. 
APPENDICES 
6.1 
APPENDIX 1: SCHEDULE OF EVENTS 
 




PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 73 
28. During the MEDI2452 (PB2452) infusion, systolic and diastolic blood pressures and heart rate will be 
collected every 5 minutes. 
g Electrocardiograms will be obtained in triplicate for all subjects at screening, before dosing (within 1 hour 
prior to the initiation of the MEDI2452 [PB2452] infusion) and at 1, 4 (±30 minutes), 5 (±10 minutes), 24, 
and 48 hours (±30 minutes) after the initiation of the MEDI2452 (PB2452) infusion and on Days 7 and 28. 
h Cardiac telemetry monitoring will begin on Day -1 approximately 12 hours prior to the initiation of the 
MEDI2452 (PB2452) infusion (Hour 0) and will continue until subject is discharged from the clinical site. 
i For Cohorts 4 through 9 only: Beginning in the morning on Day –2, ticagrelor will be administered as a single oral dose 
of 180 mg, followed by 90 mg every 12 hours for 4 additional doses through Hour 0 (ie, 5 total doses of ticagrelor with 
the 5th dose occurring simultaneously with the initiation of the MEDI2452 [PB2452] infusion). 
j For Cohorts 8 and 9 only: On Day 2, ticagrelor will be administered as an additional single dose of 180 mg, 24 hours after 
the initiation of the MEDI2452 (PB2452) infusion on Day 1 (6th ticagrelor dose). 
k For all cohorts: MEDI2452 (PB2452) or placebo will be administered at Hour 0 of Day 1. 
l For all cohorts: Blood samples for determination of serum MEDI2452 (PB2452) will be collected within 10 minutes prior 
to the initiation of MEDI2452 (PB2452) infusion (Hour 0), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours; and 7 
and 28 days after the initiation of the MEDI2452 (PB2452) infusion. 
m For Cohorts 4 through 9 only: Blood samples for determination of plasma ticagrelor and AR-C124910XX will be 
collected within 10 minutes prior to the initiation of MEDI2452 (PB2452) infusion and 5th ticagrelor dose (Hour 0) and at 
0.5, 1, 2, 3, 6, 12, and 24 hours after initiation of MEDI2452 (PB2452) infusion and 5th ticagrelor dose. 
n For Cohorts 8 and 9 only: Additional blood samples for determination of plasma ticagrelor and AR-C124910XX will be 
collected at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after Day 2 administration of ticagrelor (6th ticagrelor dose). 
o For Cohorts 4 through 9 only: Blood samples for determination of unbound plasma ticagrelor and AR-C124910XX will 
be collected before dosing (within 10 minutes prior to the initiation of MEDI2452 [PB2452] infusion and 5th 
ticagrelor dose [Hour 0]), and at 0.5, 1, 2, 3, 6, 12, and 24 hours after initiation of MEDI2452 (PB2452) infusion and 
5th ticagrelor dose. 
p For Cohorts 8 and 9 only: Additional blood samples for determination of unbound plasma ticagrelor and AR-C124910XX 
will be collected at 0.5, 1, 2, 3, 6, 12, and 24 hours after Day 2 administration of ticagrelor (6th ticagrelor dose). 
q For Cohorts 4 through 9 only: Urine samples for PK analysis of ticagrelor and AR-C124910XX 
concentrations will be collected before dosing (within 60 minutes prior to the first ticagrelor dose on Day -2), 
and 0 to 6, 6 to 12, and 12 to 24 hours after the initiation of the MEDI2452 (PB2452) infusion and the 5th 
ticagrelor dose. 
r For Cohorts 4 through 9 only: Blood samples for PD analysis (LTA/PRU/VASP testing) will be collected before dosing 
(within 60 minutes prior to first ticagrelor dose on Day -2) and again within 10 minutes prior to initiation of 
MEDI2452 (PB2452) infusion and 5th ticagrelor dose (Hour 0), and at 0.5, 1, 2, 3, 6, 12, 24, and 48 hours after initiation 
of MEDI2452 (PB2452) infusion and 5th ticagrelor dose. 
s For Cohorts 8 and 9 only: Additional blood samples for PD analysis (LTA/PRU/VASP testing) will be collected at 1, 2, 6, 
and 12 hours after Day 2 administration of ticagrelor (6th ticagrelor dose). 
t Infusion site assessments will be performed for all subjects within 15 minutes prior to the initiation of the MEDI2452 
(PB2452) infusion (Hour 0), and at 1, 3, 24, 48, and 72 hours after initiation of the MEDI2452 (PB2452) infusion and on 
Day 7. 
u For Cohorts 1 through 7 only. 
v For Cohorts 8 and 9 only. 
 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 74 
6.2 
APPENDIX 2 - LIST OF EXAMPLE INHIBITORS AND 
INDUCERS OF CYP3A4 
Strong Inhibitors (≥5-fold increase in AUC or >80% decrease in oral clearance): 
Boceprevir 
Clarithromycin 
Conivaptan 
Grapefruit juice 
Indinavir 
Itraconazole 
Ketoconazole 
Lopinavir/ritonavir 
Mibefradil 
Nefazodone 
Nelfinavir 
Posaconazole 
Ritonavir 
Saquinavir  
Telaprevir 
Telithromycin 
Voriconazole 
Strong Inducers (≥80% decrease in AUC): 
Avasimibe 
Carbamazepine 
Phenytoin 
Rifampin 
St John’s wort 
 
Note: This list is not all-inclusive. Please refer to the following website for further guidance: 
http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractio
nslabeling/ucm093664.htm 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 75 
6.3 
APPENDIX 3 - INFUSION SITE ASSESSMENT 
The investigator will assess the degree of reaction at the infusion site at scheduled time 
points during the study using the following rating scale: 
 
Adverse Events of Interest 
Mild (Grade 1) 
Moderate (Grade 
2) 
Severe (Grade 3) 
Potentially 
Life Threatening 
(Grade 4) 
Injection site adverse events 
Pain  
Does not interfere 
with activity  
Repeated use of 
non-narcotic pain 
reliever for >24 
hours or interferes 
with activity  
Any use of narcotic 
pain reliever or 
prevents daily 
activity  
Emergency room  
visit or hospitalization  
Tenderness  
Mild discomfort to 
touch  
Discomfort with 
movement  
Significant 
discomfort at rest  
Emergency room visit 
or hospitalization  
Erythema/redness*  
2.5 – 5 cm  
5.1 – 10 cm  
>10 cm  
Necrosis or exfoliative 
dermatitis  
Induration/swelling**  
2.5 – 5 cm and does 
not interfere with 
activity  
5.1 – 10 cm or 
interferes with  
activity  
>10 cm or prevents 
daily activity  
Necrosis  
* In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a continuous 
variable.  
** Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 76 
6.4 
APPENDIX 4: SECOND SYMPOSIUM ON THE 
DEFINITION AND MANAGEMENT OF ANAPHYLAXIS: 
SUMMARY REPORT—SECOND NATIONAL INSTITUTE 
OF ALLERGY AND INFECTIOUS DISEASE/FOOD 
ALLERGY AND ANAPHYLAXIS NETWORK SYMPOSIUM 
Second symposium on the definition and management of anaphylaxis: Summary report-
Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network symposium can be accessed at the following website link: 
http://www.jacionline.org/article/S0091-6749%2805%2902723-5/pdf 
Clinical criteria for diagnosing anaphylaxis are presented in Table 6.4. 
Table 6-4 
Clinical Criteria for Diagnosing Anaphylaxis 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, 
generalized hives, pruritus or flushing, swollen lips-tongue-uvula) 
 
AND AT LEAST ONE OF THE FOLLOWING: 
a. 
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, 
incontinence) 
 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to 
several hours): 
a. 
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
c. 
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. 
Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP1 
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 
Abbreviations: BP, blood pressure; PEF, peak expiratory flow. 
1 
Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less than (70 mm Hg 
+ [2 × age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years. 
 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 77 
7. 
REFERENCE LIST 
Armstrong D, Summers C, Ewart L, Nylander S, Sidaway JE, van Giezen JJ. 
Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant 
inhibition of equilibrative nucleoside transporter 1. J Cardiovasc Pharmacol Ther. 
2014;19(2):209-19. 
Bell AD, Roussin A, Cartier R, Chan WS, Douketis JD, Gupta A, et al. The use of antiplatelet 
therapy in the outpatient setting: Canadian Cardiovascular Society guidelines. Can J Cardiol. 
2011;27(2):208-21. 
Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and 
potential clinical relevance. J Am Coll Cardiol. 2014;63(23):2503-9. 
Dalén M, Ivert T, Lindvall G, van der Linden J. Ticagrelor-associated bleeding in a patient 
undergoing surgery for acute type A aortic dissection. J Cardiothorac Vasc Anesth. 
2013;27(5):e55-7. 
Doessegger L, Banholzer ML. Clinical development methodology for infusion-related 
reactions with monoclonal antibodies. Clin Transl Immunology. 2015;4(7):e39. 
Fitchett DH, Theroux P, Brophy JM, Cantor WJ, Cox JL, Gupta M, et al. Assessment and 
management of acute coronary syndromes (ACS): a Canadian perspective on current 
guideline-recommended treatment-- part 1: non-ST-segment elevation ACS. Can J Cardiol. 
2011;27 Suppl A:S387-S401. 
Godier A, Taylor G, Gaussem P. Inefficacy of platelet transfusion to reverse ticagrelor. N 
Engl J Med. 2015;372(2):196-7. 
Maillard J, Cartier Faessler V, Fontana P, Bonhomme F. Lack of effect of platelet transfusions 
and desmopressin on intracranial bleeding in a patient receiving ticagrelor. A A Case Rep. 
2015;4(12):169–71. 
Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, et al. Inhibition of 
platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared 
with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol. 
2007;50(19):1852-6. 
Storey RF. New P2Y12 Inhibitors. Heart. 2011;97:1262-1267. 


PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Protocol 
 
Page 78 
Taylor G, Osinski D, Thevenin A, Devys JM. Is platelet transfusion efficient to restore 
platelet reactivity in patients who are responders to aspirin and/or clopidogrel before 
emergency surgery? J Trauma Acute Care Surg. 2013;74(5):1367-9. 
Teng R, Carlson GF, Nylander S, Andersson TL. Effects of autologous platelet transfusion on 
platelet inhibition in ticagrelor- and clopidogrel-treated subjects. J Thromb Haemost. 2016. 
14(12):2342-52. 
van Giezen JJ, Nilsson L, Berntsson P, Wissing BM, Giordanetto F, Tomlinson W, et al. 
Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced 
receptor signaling and platelet aggregation. J Thromb Haemost. 2009;7(9):1556-65. 

SAP_001.pdf: 
PhaseBio Pharmaceuticals, Inc 
MEDI2452 (PB2452) 
Protocol No. PB2452-PT-CL-0001 
Clinical Study Report 
16.1.9 
Documentation of Statistical Methods 
This section contains the following document: 
Statistical analysis plan version 2.0 dated 12 October 2018 


 
Confidential 
 
 
PhaseBio Pharmaceuticals, Inc 
 
PB2452-PT-CL-0001 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending 
Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and 
Pharmacodynamics of MEDI2452 (PB2452) With and Without Ticagrelor 
Pretreatment in Healthy Volunteers 
12OCT2018 
Statistical Analysis Plan 
Final Version 2.0 
 
Prepared by: 
PPD 
3900 Paramount Parkway 
Morrisville, NC 27560-7200 
 
 
 
 


PhaseBio Pharmaceuticals, Inc 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
Date Issued: 12OCT2018 
  
 
 
 II 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ...................................................................................................... V 
1. 
INTRODUCTION ............................................................................................................ 7 
2. 
OBJECTIVES ................................................................................................................... 7 
2.1. PRIMARY ............................................................................................................................ 7 
2.2. SECONDARY ....................................................................................................................... 7 
2.3. EXPLORATORY ................................................................................................................... 8 
3. 
INVESTIGATIONAL PLAN .......................................................................................... 8 
4. 
GENERAL STATISTICAL CONSIDERATIONS ..................................................... 14 
4.1. GENERAL DATA PRESENTATION RULES ........................................................................... 14 
4.2. SAMPLE SIZE .................................................................................................................... 16 
4.3. RANDOMIZATION, STRATIFICATION, AND BLINDING ........................................................ 16 
4.4. BREAKING THE BLIND ...................................................................................................... 17 
4.5. REPLACEMENTS ................................................................................................................ 17 
4.6. REPEATED/UNSCHEDULED MEASUREMENTS .................................................................... 17 
4.7. HANDLING OF MISSING DATA .......................................................................................... 18 
4.8. ANALYSIS POPULATIONS .................................................................................................. 19 
5. 
SUBJECT DISPOSITION ............................................................................................. 19 
5.1. PROTOCOL DEVIATIONS AND ELIGIBILITY CRITERIA DEVIATIONS ................................... 20 
6. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................. 20 
6.1. DEMOGRAPHICS ................................................................................................................ 20 
6.2. MEDICAL HISTORY ........................................................................................................... 20 
7. 
TREATMENTS AND MEDICATIONS ....................................................................... 20 
7.1. PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 20 


PhaseBio Pharmaceuticals, Inc 
Statistical Analysis Plan, Final Version 2.0 
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Date Issued: 12OCT2018 
  
 
  III
7.2. MEDICAL AND SURGICAL PROCEDURES ........................................................................... 21 
7.3. STUDY TREATMENTS ........................................................................................................ 21 
8. 
SAFETY ANALYSIS ..................................................................................................... 22 
8.1. ADVERSE EVENTS ............................................................................................................. 23 
8.1.1. 
Incidence of Adverse Events ..................................................................................... 23 
8.1.2. 
Severity of Adverse Event.......................................................................................... 24 
8.1.3. 
Relationship of Adverse Events to Study Drug ......................................................... 25 
8.1.4. 
Adverse Events Leading to Early Discontinuation ................................................... 25 
8.1.5. 
Infusion Site Assessments .......................................................................................... 25 
8.1.6. 
Dose Limiting Toxicities ........................................................................................... 25 
8.1.7. 
Serious Adverse Events ............................................................................................. 26 
8.2. CLINICAL LABORATORY EVALUATIONS ........................................................................... 27 
8.3. VITAL SIGNS ..................................................................................................................... 28 
8.4. TWELVE-LEAD ELECTROCARDIOGRAM AND TELEMETRY MONITORING .......................... 29 
8.5. PHYSICAL EXAMINATION AND PHYSICAL MEASUREMENTS .............................................. 30 
9. 
IMMUNOGENICITY ANALYSIS ............................................................................... 31 
10. 
PHARMACOKINETIC ANALYSIS ............................................................................ 31 
10.1. 
PLASMA PHARMACOKINETICS ....................................................................................... 31 
10.1.1. 
Plasma Pharmacokinetics Concentration ............................................................. 31 
10.1.2. 
Plasma Pharmacokinetic Parameters ................................................................... 33 
10.1.3. 
Plasma Pharmacokinetic Parameters Analysis ..................................................... 36 
10.2. 
URINE PHARMACOKINETICS .......................................................................................... 36 
10.2.1. 
Urine pharmacokinetic Concentrations ................................................................ 36 
10.2.2. 
Urine Parameters .................................................................................................. 37 


PhaseBio Pharmaceuticals, Inc 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
Date Issued: 12OCT2018 
  
 
  IV 
11. 
PHARMACODYNAMIC ANALYSIS ......................................................................... 37 
11.1. 
PHARMACODYNAMIC DATA .......................................................................................... 37 
11.2. 
PHARMACODYNAMIC PARAMETERS .............................................................................. 39 
12. 
CHANGES IN THE PLANNED ANALYSIS .............................................................. 41 
13. 
INTERIM ANALYSIS ................................................................................................... 41 
14. 
REFERENCE .................................................................................................................. 42 
15. 
TABLE OF CONTENTS: TABLES, LISTINGS AND FIGURES ............................ 43 


PhaseBio Pharmaceuticals, Inc 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
Date Issued: 12OCT2018 
  
 
 
 V
List of Abbreviations 
ADA 
anti-drug antibody 
Ae 
total amount of drug excreted in urine 
AE 
adverse event 
AUC 
area under curve 
BID 
twice daily 
BLQ 
below the limit of quantification  
BMI 
body mass index 
CI 
confidence interval 
CL 
total body clearance 
CLr 
renal clearance 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Event 
CV 
coefficient of variation 
eCRF 
electronic case report form 
DLT 
dose limiting toxicity 
ECG 
electrocardiogram 
EOS 
end of study 
FA 
final-extent of platelet aggregation 
IV 
intravenous  
LTA 
light transmittance aggregometry 
MA 
maximal-extent of platelet aggregation 
NAb 
neutralizing antibody 
PD 
pharmacodynamics 
PK 
pharmacokinetics 


PhaseBio Pharmaceuticals, Inc 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
Date Issued: 12OCT2018 
  
 
  VI 
PRU 
P2Y12 reaction units 
PT 
preferred term 
QTcB 
Bazett’s-corrected QT interval 
QTcF 
Fridericia-corrected QT interval 
Rsq 
regression coefficient (R squared) 
SAE 
serious adverse event 
SAS 
statistical analysis software 
SD 
standard deviation 
SOC 
system organ class 
SRC 
safety review committee 
t1/2 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
Tmax 
time to reach the maximum plasma concentration 
VASP 
Vasodilator-stimulated phosphoprotein 
Vd 
volume of distribution 
λz 
terminal phase rate constant 
 
 
 


PhaseBio Pharmaceuticals, Inc 
 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
 
Date Issued: 12OCT2018 
 
 7
1. Introduction 
MEDI2452 (PB2452) is a specific and selective neutralizing antibody fragment that binds 
ticagrelor and AR-C124910XX, the major active circulating ticagrelor metabolite, with 
high affinity. MEDI2452 (PB2452) is intended to reverse the antiplatelet effects of 
ticagrelor in patients who experience major bleeding or who require urgent surgery or 
intervention, serious but rare conditions that represent an unmet medical need. 
This is the first-in-human study with MEDI2452 (PB2452) and is designed to provide 
initial safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) data 
regarding MEDI2452 (PB2452) for future clinical studies. 
This statistical analysis plan (SAP) reflects the protocol amendment 5 dated 03 August, 
2018.  
2. Objectives 
2.1. Primary 
The primary objectives of this study are: 
• To evaluate the safety and tolerability of single ascending intravenous (IV) doses of 
MEDI2452 (PB2452) with or without ticagrelor 
• To evaluate the effectiveness of single ascending doses of MEDI2452 (PB2452) 
dose on ticagrelor antiplatelet activity using light transmittance aggregometry 
(LTA) 
2.2. Secondary 
The secondary objectives of the study are: 
• To determine the PK of ascending doses of IV MEDI2452 (PB2452) in the 
presence and absence of ticagrelor 
• To determine the PK of ticagrelor and its active metabolite AR-C124910XX in the 
presence and absence of MEDI2452 (PB2452) 


PhaseBio Pharmaceuticals, Inc 
 
Statistical Analysis Plan, Final Version 2.0 
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Date Issued: 12OCT2018 
 
 8
• To assess the effectiveness of a single IV MEDI2452 (PB2452) dose in reversing 
ticagrelor antiplatelet activity by measuring P2Y12 reaction units (PRU) with 
VerifyNow™ P2Y12 assay and platelet reactivity index (PRI) with vasodilator 
stimulated phosphoprotein (VASP) phosphorylation assay by enzyme-linked 
immunosorbent assay (ELISA) 
• To evaluate the PK and PD of restarting a single dose of oral ticagrelor 24 hours 
after MEDI2452 (PB2452) administration if a sixth dose of ticagrelor is given 
• To evaluate the immunogenicity potential of MEDI2452 (PB2452) 
2.3. Exploratory 
The exploratory objective is to evaluate the effect of MEDI2452 (PB2452) on the PK 
profile of unbound ticagrelor and unbound AR-C124910XX plasma concentrations. 
3. Investigational Plan 
This is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled, single 
ascending dose, sequential group study to evaluate the safety, tolerability, PK, and PD of 
MEDI2452 (PB2452) with and without ticagrelor pretreatment when administered to 
healthy male and female subjects. All references to study drug within this statistical 
analysis plan (SAP) apply to MEDI2452 (PB2452) or matching placebo. 
This study will have up to 10 cohorts and up to a total of 68 subjects with either 4 or 8 
subjects in each cohort. The starting dose of MEDI2452 (PB2452) will be 100 mg and the 
planned doses for subsequent cohorts are 300, 1000, 3000, 9000, and 18000 mg. Other 
intermediate doses may also be tested but will not exceed 1800 mg. 
The study will consist of a screening period (Days –45 to –4), check-in/pretreatment 
(Day -3 to Day -1), an in-house treatment period (Days 1 through 3 [Cohorts 1 through 8] 
or 4 [Cohorts 9 and 10]), and follow-up visits (Days 4, 7, and 28 [+2 days]). Subjects will 
receive an IV dose of study drug on Day 1. 


PhaseBio Pharmaceuticals, Inc 
Statistical Analysis Plan, Final Version 2.0 
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Date Issued: 12OCT2018 
 9
On Day 1, subjects who meet all the inclusion criteria and none of the exclusion criteria 
will be randomly assigned to receive MEDI2452 (PB2452) or placebo in a ratio of 3:1 in 
all treatment cohorts as described below and as summarized in Table 3-1. 
Table 3-1 
Summary of Treatment per Cohort 
Cohort 
Pre-MEDI2452 (PB2452) ticagrelor 
dosing to steady state 
(180 mg + 90 mg bid for 5 doses total) 
MEDI2452 
(PB2452) Dose 
(mg) 
Number of subjects 
MEDI2452 
(PB2452):placebo 
1
100
3:1
2
300
3:1
3
1000
3:1
4 
180 mg + 90 mg bid 
1000 
6:2 
5 
180 mg + 90 mg bid 
3000 
6:2 
6 
180 mg + 90 mg bid 
9000 
6:2 
7 
180 mg + 90 mg bid 
18000 
6:2 
8 
180 mg + 90 mg bid 
18000 
6:2 
9 
180 mg + 90 mg bid 
18000 
3:1 or 6:2* 
10 
180 mg + 90 mg bid 
18000 
3:1 or 6:2* 
Abbreviations: bid, twice daily. 
*Initially the cohort size will be 4 subjects (3:1); if needed for confirmation of PK/PD an additional 4 subjects
(3:1) will be randomized in that same cohort.
Cohorts 1 to 3: 
For the initial cohort (Cohort 1), 4 healthy subjects will be randomly assigned in a 3:1 ratio 
of active treatment to placebo (3A:1P) to receive a single 100-mg IV dose of study drug 
over 30 minutes. For the second cohort (Cohort 2), 4 healthy subjects will be randomly 
assigned (3A:1P) to receive a single 300-mg IV dose of study drug over 30 minutes. For 
the third cohort (Cohort 3), 4 healthy subjects will be randomly assigned (3A:1P) to 
receive a 1000-mg IV dose of study drug over 30 minutes. 
Cohorts 4 to 6: 


PhaseBio Pharmaceuticals, Inc 
 
Statistical Analysis Plan, Final Version 2.0 
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Date Issued: 12OCT2018 
 
 
 
10
Provided no safety concerns arise in Cohorts 1 through 3, 8 subjects in each of Cohorts 4 
through 6 will be randomly assigned in a 3:1 ratio (6A:2P) to receive a single IV dose of 
study drug simultaneous with the 5th dose of ticagrelor pretreatment. For ticagrelor 
pretreatment, subjects will receive an oral loading dose of 180-mg ticagrelor in the 
morning (Day -2), followed by 90-mg ticagrelor orally every 12 hours for 4 additional 
doses, prior to administration of a single IV dose of study drug simultaneous with the 5th 
ticagrelor dose (Day 1). Subjects in each of Cohorts 4 through 6 will receive ticagrelor 
pretreatment, as described above, and a single IV dose of 1000, 3000, or 9000 mg of study 
drug, respectively, over 30 minutes. Cohorts 4 through 6 will be dosed sequentially 
following the safety and dose-escalation assessment of each preceding dose cohort. 
Cohorts 7 to 10: 
For Cohorts 7 to 10, following ticagrelor pretreatment, subjects will be randomly assigned 
in a 3:1 ratio (3A:1P or 6A:2P) to receive a single IV dose of study drug. The IV infusion 
of study drug will be initiated 2 hours after the 5th ticagrelor dose. The duration of the 
infusion will be determined upon analysis of data from prior cohorts, and will range 
between 30 minutes and 24 hours. Total doses to be administered in these cohorts will be 
determined based upon analysis of data from prior cohorts, and will be within the range of 
9000-18000 mg.  
The overall Study design is presented in Figure 3-1.  


PhaseBio Pharmaceuticals, Inc 
 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
 
Date Issued: 12OCT2018 
 
 
 
11
Figure 3-1 
Study Flow Diagram 
 
 
Schedule of Events is presented in Table 3-2. 
 
 
Screening 
Days -45 to -4 
Check-in/Pre-
treat 
Days -3 to -1 
Day -3: Check-in 
Cohorts 4 - 10 
Day -2: ticagrelor 
pre-treat  
Cohorts 4 - 10 
Day -1: Check-in 
Cohorts 1 - 3 
Randomization 
Day 1 
Treatment 
Days 1 to 4 
Day 1: MEDI2452 
(PB2452) or 
placebo 
Cohorts 1 - 10 
Discharge 
Days 3, 4 
Day 3: Cohorts 
1 – 8 
Day 4: Cohort 
9 & 10  
 


PhaseBio Pharmaceuticals, Inc 
 
Statistical Analysis Plan, Final Version 2.0 
PB2452-PT-CL-0001 
 
Date Issued: 12OCT2018 
 
 
 
12
Table 3-2 
Schedule of Events 
Procedure 
Screening 
Check-in/ 
Pretreatment 
Treatment 
 
Follow
-upa 
EOSa 
Study Day(s) –45 to –4 
–3 
-2 
–1 
1 
2 
3 
4/FU 
7 
28 (+2 
days) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xc 
 
Xd 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Urine drug screen (includes 
cotinine) 
X 
Xc 
 
Xd 
 
 
 
 
 
 
Urine alcohol 
X 
Xc 
 
Xd 
 
 
 
 
 
 
Serum pregnancy test 
X 
Xc 
 
Xd 
 
 
 
 
 
X 
Serology testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinic 
 
Xc 
 
Xd 
 
 
 
 
 
 
Physical examinatione 
X 
Xc 
 
Xd 
 
 
X 
 
X 
X 
Vital sign measurementsf 
X 
Xc 
 
Xd 
X 
X 
X 
X 
X 
X 
12-lead electrocardiogramg 
X 
 
 
 
X 
X 
X 
 
X 
X 
Cardiac telemetry monitoringh 
 
X 
 
X 
X 
X 
X 
 
 
 
Clinical laboratory testing 
X 
Xc 
 
Xd 
 
 
X 
 
X 
X 
Randomization 
 
 
 
 
X 
 
 
 
 
 
Drug administration 
 
 
 
 
 
 
 
 
 
 
Ticagrelor 
 
 
Xi 
Xi 
Xi 
 
 
 
 
 
MEDI2452 (PB2452)/Placebok 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK blood samplingl 
 
 
 
 
 
 
 
 
 
 
Plasma MEDI2452 (PB2452)l 
 
 
 
 
X 
X 
X 
Xaa 
X 
X 
Plasma 
ticagrelor/AR-C124910XXl 
 
 
 
 
X 
X 
Xx 
X 
 
 
Free plasma 
ticagrelor/AR-C124910XXl 
 
 
 
 
X 
X 
Xx 
X 
 
 
PK urine samplingq 
 
 
X 
 
X 
X 
X 
 
 
 
PD sampling (LTA/PRU/VASP)r 
 
 
X 
 
X 
X  
X 
 
 
 
Infusion site assessmentt 
 
 
 
 
X 
X 
X 
X 
X 
 
Serum immunogenicity 
 
Xc 
 
Xd 
 
 
 
 
X 
Xw 
Adverse events 
 
Xc 
Xc 
X 
X 
X 
X 
X 
X 
X 
Discharge from clinic 
 
 
 
 
 
 
Xu 
X 
 
 


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Abbreviations: BID, twice daily; EOS, end-of-study; FU, follow-up; LTA, light transmittance aggregometry; 
PD, pharmacodynamic; PK, pharmacokinetic; PRU, P2Y12 reaction units; VASP, vasodilator stimulated 
phosphoprotein. 
a Follow-up visits will be conducted as outpatient. 
c Cohorts 4 through 10 only. 
d Cohorts 1 through 3 only. 
e Full physical examination (including height, weight, and body mass index calculation) will be performed at 
screening and Day 28 only. Brief physical examinations will be performed at all other time points. 
f Vital sign measurements (systolic and diastolic blood pressures, oral body temperature, respiratory rate, and 
heart rate) will be collected at screening, check-in, before dosing (30 minutes prior to the initiation of the 
study drug  infusion) and at 0.5, 0.75, 1, 2, 4, 8, and 24 hours after the initiation of the study drug  infusion, 
and at 30, 36, 42, and 48 hours after the initiation of the study drug infusion and on Days 4, 7, and 28. 
Starting with the 1 hour after initiation of the study drug timepoint for the collection of vitals a ±5 minute 
window will be permitted.  During the initial 30 minutes of study drug infusion, systolic and diastolic blood 
pressures and heart rate will be collected every 5 minutes. 
g Electrocardiograms will be obtained in triplicate for all subjects at screening, before dosing (within 1 hour 
prior to the initiation of the study drug infusion) and at 1 (±10 minutes), 4 (±10 minutes), 5 (±10 minutes), 
24 (±30 minutes), and 48 hours (±30 minutes) after the initiation of the study drug infusion and on Days 7 
and 28. 
h Cardiac telemetry monitoring will begin on Day -1 approximately 12 hours prior to the initiation of the 
study drug infusion (Hour 0) and will continue until the subject is discharged from the clinical site for 
Cohorts 1-10.  For Cohorts 4-10, cardiac telemetry monitoring will begin on Day-3 (check in) 
approximately 12 hours prior to the first dose of Ticagrelor and will be removed once dosed with the initial 
dose of Ticagrelor. 
i For Cohorts 4 through 6 only: Beginning in the morning on Day –2, ticagrelor will be administered as a 
single oral dose of 180 mg, followed by 90 mg every 12 hours for 4 additional doses through Hour 0 (i.e., 5 
total doses of ticagrelor).  For Cohorts 7 through 10 only: Beginning in the morning on Day –2, ticagrelor 
will be administered as a single oral dose of 180 mg, followed by 90 mg every 12 hours for 4 additional 
doses through to Hour -2 (two hours prior to dosing at Hour 0) (i.e., 5 total doses of ticagrelor). 
k For all cohorts: MEDI2452 (PB2452) or placebo will be administered at Hour 0 of Day 1. 
l For timing of pharmacokinetic plasma samples for each cohort, refer to section 3.5.1 of the protocol.  
q For Cohorts 4 through 10 only: Urine samples for PK analysis of ticagrelor and AR-C124910XX 
concentrations will be collected before dosing (within 60 minutes prior to the first ticagrelor dose on Day -
2), and 0 to 6, 6 to 12, 12 to 24 and 24 to 48 hours after the initiation of the study drug infusion.  
r For timing of pharmacodynamic samples for each cohort, refer to section 3.5.2 of the protocol.  
t Infusion site assessments will be performed for all subjects within 15 minutes prior to the initiation of the 
study drug infusion (Hour 0), and at 1, 3, 24, 48, and 72 hours after initiation of the study drug infusion and 
on Day 7.   
u For Cohorts 1 through 8 only. 
w   Subject may be required to return to collect additional follow-up samples should the sample collected at day 
28 test positive for anti-drug antibody development. These visits may be done approximately 3 months after 
their final visit and approximately every 6 months thereafter or until their levels return to baseline.  
x    For Cohorts 4-10: Blood samples for determination of plasma ticagrelor and AR-C124910XX AND 
unbound plasma ticagrelor and AR-C124910XX will be collected 48 hours after the initiation of the study 
drug infusion. 
aa Omitted for Cohorts 7-10. 
Note:  Footnotes b, j, m, n, o, p, s, v, y, z are intentionally omitted.   


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4. General Statistical Considerations 
All statistical analyses will be conducted using statistical analysis system SAS® software 
(SAS Institute, Cary, NC USA) Version 9.3 or higher (version to be delineated in the 
clinical study report [CSR]). All tables and data listings will appear in landscape format 
employing Courier New 9-point font. 
4.1. General Data Presentation Rules 
All data will be provided in individual by-subject listings. 
Data from subjects excluded from an analysis population will be presented in the data 
listings but not included in the calculation of summary statistics. 
Data from subjects receiving placebo will be pooled across cohorts for all presentations. 
Unless otherwise noted, the following treatment groups will be used in summaries: 
• 100 mg PB2452 (C1) 
• 300 mg PB2452 (C2) 
• 1000 mg PB2452 (C3) 
• Placebo C1-C3 
• 1000 mg PB2452 (C4) 
• 3000 mg PB2452 (C5) 
• 9000 mg PB2452 (C6) 
• Placebo C4-C6 
• 18000 mg PB2452 (C7) 
• 18000 mg PB2452 (C8) 
• 18000 mg PB2452 (C9) 


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• 18000 mg PB2452 (C10) 
• Placebo C7-C10 
• All Placebo (for safety summaries only) 
• All PB2452 (for safety summaries only) 
• All subjects 
where ‘C’ means ‘Cohort’. 
Demographic data, baseline characteristics, adverse events (AEs), laboratory tests, vital 
signs, 12-lead electrocardiogram (ECG) measurements, and subject disposition will be 
summarized descriptively. 
Unless otherwise noted, the summary of the continuous variables will include the number 
of subjects with non-missing data (n), mean, standard deviation (SD), median, minimum, 
and maximum. Categorical variables will be summarized descriptively by their counts and 
associated percentages. Percentages will be calculated using the number of subjects within 
a summary group as the denominator. 
Minimum and maximum values will be presented as the same precision as the original 
value. Means and medians will be presented as 1 decimal place greater than the precision 
of the original value. Standard deviations will be presented as 2 decimal places greater than 
the precision of the original value. Percentages for summarizing categorical data will be 
presented with 1 decimal place. If the percentage value is less than 0.1, then "<0.1" will be 
displayed.  
Unless specified otherwise, baseline for safety analyses is defined as the last non-missing 
measurement (including repeated and unscheduled measurements) prior to the first study 
drug administration; baseline for PD analyses is defined as the last non-missing 
measurement (including repeated and unscheduled measurements) prior to the first 
ticagrelor administration.  


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Listings will be sorted by treatment group and subject identifier.  
4.2. Sample Size 
The sample size (N) of up to 68 for this study is based on clinical and practical 
considerations and not on a formal statistical power calculation. The sample size is 
considered sufficient to adequately assess the safety, PK, and PD profiles of MEDI2452 
(PB2452) and the PK and PD profiles of ticagrelor. 
4.3. Randomization, Stratification, and Blinding 
Randomization to MEDI2452 (PB2452) or placebo within each one of the ten cohorts will 
be based on a randomization schedule prepared by PPD before the start of the study using 
SAS® software. The randomization scheme within each cohort is specified in Table 3-1. 
There will be no stratification factors in the randomization. 
This is a double-blind study. Neither the subjects nor the investigator will be aware of the 
treatment assignment. Blinding will be maintained throughout the study by use of active 
and placebo dosage forms of similar appearance once prepared. To maintain the blind, only 
designated pharmacy staff at the clinical site will have access to the randomization code 
and will prepare each dose for each subject. The PK and PD samples will be shipped to the 
designated laboratories who are only responsible for analyzing the PK and PD samples and 
will not be involved in any other study activities. In order to prepare preliminary 
summaries of safety, PK, and/or PD data as needed to make timely decisions regarding 
adjustment of study procedures, dosing regimens, or potentially early termination of the 
study, certain designated staff at PhaseBio and PPD who are not involved in the study 
design or conduct may be unblinded during the conduct of the study (study director, a 
single biostatistician, bioanalytical scientist, and programming team) before data is more 
generally unblinded. These summaries will not reveal individual subjects’ treatment 
assignments. All other members of PhaseBio research and development and members from 
PPD will remain blinded. Access to the randomization code will be strictly controlled 
according to PPD and PhaseBio standard operating procedures. 


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The scheduled unblinding event to all study members will occur after the database is 
locked (hard-locked). 
4.4. Breaking the Blind 
A subject may be unblinded in the event of a dose limiting toxicity (DLT), serious AE 
(SAE), or other event, or if there is a medical emergency where the identity of the drug 
must be known to properly treat a subject. A cohort may be unblinded to determine if dose 
escalation to the next dose level will terminate. If a subject becomes seriously ill during the 
study, the blind will be broken only if knowledge of the administered study drug will affect 
that subject’s treatment options. In the event of a medical emergency requiring 
identification of the study drug administered to an individual subject, the investigator will 
make every attempt to contact the medical monitor to explain the need for opening the 
code within 24 hours of opening the code. The investigator will be responsible for 
documenting the time, date, reason for the code break, and the names of the personnel 
involved.  
4.5. Replacements 
At the discretion of the investigator after consultation with the sponsor, any subject who 
withdraws before completing the study, for reasons other than a DLT may be replaced. 
Any replacement subject will be assigned to receive the same treatment as the subject he or 
she is replacing. 
4.6. Repeated/Unscheduled Measurements 
For safety summary tables summarized by time point, excluding baseline, if there are 
repeated measurements for a subject at a scheduled time point, the original scheduled 
measurement at that time point will be used in the summary tables.  
Unscheduled results, i.e. results that are not from a scheduled event or repeated 
measurements for a scheduled event, will not be included in the summary tables except for 
determining baseline, but will be presented in data listings.  


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4.7. Handling of Missing Data 
Subjects with missing data for some summary statistic will not be included in the 
calculation of that statistic but are eligible for inclusion in any other summary statistic for 
which they provide data. For the purpose of determining inclusion of AEs in 
treatment-emergent AE (TEAE) summary tables, incomplete or missing AE onset and end 
dates will be imputed as follows: 
Incomplete or missing onset dates (where UK and UNK indicate unknown or missing day 
and month, respectively): 
• UK-MMM-YYYY: If the month and year are different from the month and year of 
the dose of study drug, assume 01-MMM-YYYY. If the month and year are the 
same as the dose of study drug month and year, and the end date (after any 
imputation) is on or after the dose of study drug, then assume the date of the dose 
of study drug. If the month and year are the same as the dose of study drug month 
and year and the end date (after any imputation) is prior to the dose of study drug, 
then assume the end date for the onset date.  
• DD-UNK-YYYY or UK-UNK-YYYY: If the year is different from the year of 
dose of study drug, assume DD-JAN-YYYY or 01-JAN-YYYY of the onset year, 
respectively. If the year is the same as the dose of study drug year, and the end date 
(after any imputation) is on or after the dose of study drug, then assume the date of 
the dose of study drug. If the year is the same as the dose of study drug, and the end 
date (after any imputation) is prior to the dose of study drug, then assume the end 
date for the onset date.  
• Missing onset date: If the onset date is completely missing and the end date (after 
any imputation) is on or after the dose of study drug, then assume the date of the 
first dose of study drug. If the end date (after any imputation) is prior to the dose of 
study drug, then assume the end date for the onset date. 


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Incomplete or missing end dates (where UK and UNK indicate unknown or missing day 
and month respectively):  
• UK-MMM-YYYY: Assume the last day of the month; 
• DD-UNK-YYYY or UK-UNK-YYYY: Assume DD-DEC-YYYY or 31-DEC-YYYY, 
respectively; 
• Missing end date: Assume 31-DEC-YYYY, where YYYY is the year of the dose of 
study drug. 
An AE with missing onset time but with an onset date the same as the dosing date of study 
drug will be classified as treatment-emergent, unless the AE was reported pre-dose with 
the same or worse intensity or frequency. 
Medications with missing start time but with a start date the same as the dosing date of 
study drug will be considered as being taken on or after the initiation of study drug, unless 
the electronic case report form (eCRF) question “Was the medication/therapy taken prior 
to the study” is answered as “Yes” which is considered as being taken prior to the initiation 
of study drug. 
4.8. Analysis Populations 
The Randomized population includes all subjects who are randomized. 
The Safety population includes all subjects who receive any amount of study drug. 
The PK population includes subjects who receive at least 1 dose of study drug and have at 
least 1 measurable PK concentration. 
The PD population includes subjects who receive at least 1 dose of ticagrelor and have at 
least 1 measurable post dose LTA value. 
5. Subject Disposition 
Screen failures will be listed together with screening date and reason for failure. 


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Subject disposition data including screening date, randomization information, reasons for 
subjects excluded from the analysis populations, and study completion will be presented in 
data listings. The frequency and percentage of subjects who completed and discontinued 
from the study together with reason for premature withdrawal, and subjects who completed 
and discontinued the study drug together with reason for not completing the study drug 
will be summarized for the randomized subjects by treatment group and overall. Subjects 
included in each analysis population will be summarized for each treatment group and 
overall.  
5.1. Protocol Deviations and Eligibility Criteria Deviations 
Protocol deviations will be listed. Eligibility with regards to inclusion and exclusion 
criteria will be listed. 
6. Demographics and Baseline Characteristics 
6.1. Demographics 
Demographic information will be presented in a listing and summarized in a table. 
Descriptive statistics will be calculated for age (years, calculated as the integer part of 
[date of informed consent - date of birth]/365.25), screening weight, height, and body mass 
index (BMI). Frequency counts and percentages will be tabulated for sex, race, and 
ethnicity. The summaries will be presented by treatment groups (as defined in Section 4.1) 
and overall for the Safety population.  
6.2. Medical History 
The medical history findings will be presented in a listing. 
7. Treatments and Medications  
7.1. Prior and Concomitant Medications 
Information about prior medications taken by the subject within the 30 days before he or 
she provides informed consent will be recorded in the subject’s eCRF.  


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Prior medications are defined as medications taken prior to the initiation of study drug. 
Concomitant medications are defined as medications that were taken on or after the 
initiation of study drug, A medication can be considered as both prior and concomitant if 
the medication is taken prior to the initiation of study drug and continued into the treatment 
period. 
Prior and concomitant medications will be coded using the latest version of the World 
Health Organization Drug Dictionary (version March 2018 or later) and presented in a 
listing. 
7.2. Medical and Surgical Procedures 
Medical and surgical procedures will be presented in a listing. 
7.3. Study Treatments 
The dosing regimens of study drugs in each cohort are as follows: 
• Cohort 1: single 30-minute IV infusion of 100 mg MEDI2452 (PB2452) or matching 
placebo in the morning on Day 1 
• Cohort 2: single 30-minute IV infusion of 300 mg MEDI2452 (PB2452) or matching 
placebo in the morning on Day 1 
• Cohort 3: single 30-minute IV infusion of 1000 mg MEDI2452 (PB2452) or matching 
placebo in the morning on Day 1 
• Cohort 4: simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 
1000 mg MEDI2452 (PB2452) or matching placebo on Day 1 
• Cohort 5: simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 
3000 mg MEDI2452 (PB2452) or matching placebo on Day 1 
• Cohort 6: simultaneous with the 5th ticagrelor dose, a single 30-minute IV infusion of 
9000 mg MEDI2452 (PB2452) or matching placebo on Day 1 


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• Cohort 7: 2 hours following the 5th ticagrelor dose, a single IV infusion of 18000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1. The single IV infusion of 18000 
mg MEDI2452 (PB2452) or matching placebo will be delivered as a 3000 mg loading 
dose (41.7 mL) in the first 5 minutes at a rate of 500 mL/hour, followed by a 15000 mg 
maintenance dose (208.3 mL) delivered over the remaining 7 hours and 55 minutes at a 
rate of 26.3 mL/hour. The final volume is 250 mL (Memo Re: PB2452-PT-CL-0001 
Cohort 7 Dosing Regimen). 
• Cohort 8: 2 hours following the 5th ticagrelor dose, a single IV infusion of 18000 mg 
MEDI2452 (PB2452) or matching placebo on Day 1. The single IV infusion of 18000 
mg MEDI2452 (PB2452) or matching placebo will be delivered as a 6000 mg loading 
dose (83.3 mL) in the first 15 minutes at a rate of 333 mL/hour, followed by a 6000 mg 
dose (83.3 mL) over the next 3 hours at a rate of 27.7 mL/hour, and followed by a 6000 
mg dose (83.4 mL) over the remaining 8 hours and 45 minutes at a rate of 9.53 
mL/hour. The final volume is 250 mL (Memo Re: PB2452-PT-CL-0001 Cohort 8 
Dosing Regimen). 
• Cohorts 9 and 10: 2 hours following the 5th ticagrelor dose, a single IV infusion of 
18000 mg MEDI2452 (PB2452) or matching placebo on Day 1. The single IV infusion 
of 18000 mg MEDI2452 (PB2452) or matching placebo will be delivered as a 6000 mg 
loading dose (83.3 mL) in the first 15 minutes at a rate of 333 mL/hour, followed by a 
6000 mg dose (83.3 mL) over the next 4 hours at a rate of 20.8 mL/hour, and followed 
by a 6000 mg dose (83.4 mL) over the remaining 12 hours and 5 minutes at a rate of 
6.9 mL/hour. The final volume is 250 mL (Memo Re: PB2452-PT-CL-0001 Cohorts 9 
and 10 Dosing Regimens). 
Study drug administration data will be presented in a listing.  
8. Safety Analysis 
Safety and tolerability will be assessed by monitoring and recording of AEs, clinical 
laboratory test results (hematology, coagulation, serum chemistry, and urinalysis), vital 


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sign measurements (systolic and diastolic blood pressures, oral body temperature, 
respiratory rate, and heart rate), ECG results, cardiac telemetry, and physical examination 
findings. 
8.1. Adverse Events 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug-related.  
A TEAE is defined as any event not present before exposure to study drug or any event 
already present that worsens in intensity or frequency after the exposure. For analysis 
purposes, TEAEs are the events with onset on or after initiation of study drug. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDra), version 21.0 or higher, by system organ class (SOC) and preferred term (PT). 
All summary tables except from the overall summary table will be based on TEAEs. The 
SOCs will be displayed in descending order of overall frequency and then alphabetically. 
The PTs will be displayed in descending order of overall frequency and then alphabetically 
within SOC. A subject with 2 or more AEs within the same level of summarization will be 
counted only once in that level using the most severe (for the severity table) or most related 
(for the relationship to study drug table) incident.  
Summary tables will be presented by treatment groups as defined in Section 4.1. 
Percentages will be based upon the number of subjects in the safety population overall and 
within each treatment group.  
8.1.1. Incidence of Adverse Events 
All AEs will be presented in a data listing, and all TEAEs will be presented in a summary 
table by SOC, PT treatment group and overall. Additional table of TEAEs will be 
presented in a summary by PT only. 
An overall summary table will be created presenting the number of events and percentage 
of subjects with: 


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• Any TEAE 
• Any study-drug-related TEAE 
• Any severe TEAE  
• Any severe study-drug-related TEAE  
• Any serious adverse event (SAE) 
• Any treatment-emergent, study-drug-related SAE 
• Any AE leading to early study discontinuation 
• Any DLT 
• Any death 
The definition of DLT is defined in Section 8.1.6. For the purpose of above summary, a 
study-drug-related or ticagrelor-related AE is an AE with definite, probable, possible, or 
missing relationship to the study drug or ticagrelor respectively on eCRF.  
8.1.2. Severity of Adverse Event 
The severity (or intensity) of an AE refers to the extent to which it affects the subject’s 
daily activities and will be classified as mild, moderate, or severe. The TEAEs will be 
summarized by SOC, PT, severity (including category ‘Missing’ for events with missing 
severity assessment on eCRF) and treatment group. A subject with 2 or more TEAEs 
within the same level of summarization with at least 2 different non-missing severities will 
be counted only once using the most severe AE.  
The Common Terminology Criteria for Adverse Event (CTCAE) v5 grading scale will be 
used by the SRC to assess all infusion-related reactions for the purposes of determining 
whether premedication to mitigate future potential infusion-related reactions is required for 
subsequent study subjects. Details of infusion-related reactions are provided in Section 
8.1.5 Additionally, CTCAE v5 will be used by the SRC to assess all AEs and laboratory 


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abnormalities for the purposes of determining whether a DLT and/or stopping criteria have 
been reached. Details of the definition of DLT are provided in Section 8.1.6. 
8.1.3. Relationship of Adverse Events to Study Drug 
The relationship of AE to study drug and ticagrelor (if applicable) will be classified by the 
Investigator as unrelated, possible, probable, and definite. TEAEs will be summarized by 
SOC, PT, relationship to PB2452 and ticagrelor (if applicable), including category 
‘Missing’, and treatment group. A subject with 2 or more TEAEs within the same level of 
summarization will be counted only once in that level using the most related incident.  
8.1.4. Adverse Events Leading to Early Discontinuation 
All AEs that lead to early discontinuation will be presented in a listing. 
8.1.5. Infusion Site Assessments 
The infusion site will be examined by the investigator or designee for pain, tenderness, 
erythema/redness, and induration/swelling at Day 1 (within 15 minutes prior to the 
initiation of the MEDI2452 [PB2452] infusion [Hour 0], and at 1, 3 hours after initiation of 
the MEDI2452 [PB2452] infusion), at Day 2, Day 3, Day 4 and Day 7.  
The infusion site assessments will not be recorded in the database and will only be kept in 
the source documents. Any infusion-related reaction will be documented as an AE for each 
individual symptom. The individual symptom will be noted in the AE comments data field. 
Assessment of severity of the infusion-related reactions be classified as mild, moderate, or 
severe, and will also be assessed according to CTCAE v5 grading scale and should be 
followed until resolution.  
8.1.6. Dose Limiting Toxicities 
The SRC will review all AEs and all laboratory and ECG abnormalities according to 
CTCAE v5 to determine whether a DLT has been identified in a subject who is confirmed 
to have received MEDI2452 (PB2452). If the SRC determines that an AE is related to 


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administration of ticagrelor (Cohorts 4-10), or another confirmed cause, the AE will not be 
considered a DLT.  
The SRC will provide an external spreadsheet which contains all DLT events and this 
external spreadsheet will be used in the summaries and listings. 
Definitions for DLT are described below: 
1. A DLT is defined as any AE that is assessed as grade 2 or higher based on the 
CTCAE v5 grading scale and has occurred in a subject confirmed to have received 
MEDI2452 (PB2452). 
2. A DLT is defined as any grade 2 or higher laboratory abnormality (outside the clinical 
laboratory normal reference range) that occurs in a subject confirmed to have received 
MEDI2452 (PB2452). [Note: For a grade 2 electrolyte abnormality that spontaneously 
resolves to ≤ grade 1 (without intervention) within 24 hours, the SRC may decide to 
exempt the laboratory abnormality from being considered a DLT]. 
3. A DLT is defined as any TEAE that leads to study withdrawal of a subject confirmed 
to have received MEDI2452 (PB2452).  
8.1.7. Serious Adverse Events 
An AE or suspected adverse reaction is considered a SAE/suspected unexpected serious 
adverse reaction if, in the view of either the investigator or sponsor, it results in any of the 
following outcomes: 
• Death 
• Life-threatening AE 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital anomaly or birth defect 


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All SAEs and suspected unexpected serious adverse reactions including deaths will be 
presented in a data listing. 
8.2. Clinical Laboratory Evaluations 
Blood samples for laboratory safety tests (hematology, coagulation and serum chemistry) 
and urine samples for urinalysis will be collected at Screening, Day -3 (Cohorts 4 through 
10 only), Day -1 (Cohorts 1 through 3 only), Day 3 (Cohorts 1 through 8 and 10 only), 
Day 4 (Cohort 9 only if a 6th dose of ticagrelor was given on Day 2), Day 7, and Day 
28/EOS. 
Serology testing will be performed at Screening.  
Urine drug, alcohol screen, and Hemoglobin A1C for diabetic patients, will be performed 
at Screening, Day -3 (Cohorts 4 through 10 only), and Day -1 (Cohorts 1 through 3 only).  
Serum pregnancy test for female subjects will be performed at Screening, Day -3 (Cohorts 
4 through 10 only), Day -1 (Cohorts 1 through 3 only), and Day 28/EOS.  
Stool occult blood test will be performed at Screening for Cohort 10 only. 
The following clinical laboratory assessments will be performed: 
Hematology: Hematocrit, hemoglobin, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, mean corpuscular volume, platelet count, red blood cell count, 
and total and differential leukocyte count 
Coagulation: Activated partial thromboplastin time, international normalized ratio, partial 
thromboplastin time, and prothrombin time 
Serum Chemistry: Alanine aminotransferase, albumin, alkaline phosphatase, aspartate 
aminotransferase, bicarbonate, bilirubin (total and direct), blood urea nitrogen, calcium, 
chloride, cholesterol (total, high-density lipoprotein, and calculated low-density 
lipoprotein), creatine phosphokinase, creatinine, gamma-glutamyltransferase, globulin, 
glucose, lactate dehydrogenase, magnesium, phosphorus, potassium, sodium, thyroid 
stimulating hormone (Screening only), total protein, triglycerides, and uric acid 


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Urinalysis: Appearance, bilirubin, color, glucose, ketones, leukocyte esterase, reflex 
microscopy (performed if dipstick is positive for protein or blood value of 1+ or greater; 
and includes bacteria, casts, crystals, epithelial cells, red blood cells, and white blood 
cells), nitrites, occult blood, pH, protein, specific gravity, turbidity, and urobilinogen 
Serology: Hepatitis B surface antigen, hepatitis C virus antibody, and human 
immunodeficiency virus types 1 and 2 antibodies 
Other analyses: Urine drug screen (amphetamines, barbiturates, benzodiazepines, 
cannabinoids, cocaine, cotinine, methylenedioxymethamphetamine, opiates, phencyclidine, 
propoxyphene, and tetrahydrocannabinol), urine alcohol. Follicle-stimulating hormone and 
serum pregnancy test (human chorionic gonadotropin) will be collected for female 
subjects. 
The investigator will determine whether any of the abnormally high or low results are 
clinically significant or not clinically significant.  
The hematology and coagulation, chemistry, and urinalysis test results will be presented in 
the data listings sorted by treatment group, subject, laboratory test, and sample collection 
date/time. Values that are outside of the normal range as well as the clinically significance 
information will be flagged in the listings. Actual results and change from baseline will be 
summarized for the safety population. Refer to Section 4.1 for the definition of baseline for 
this summary. Shift tables will be generated for the safety population.  
All other laboratory tests will be presented in a data listing sorted treatment group, subject, 
laboratory test category, laboratory test, and sample collection date/time. 
8.3. Vital Signs  
Vital signs will be measured at Screening, Day -3 (Cohorts 4 through 10 only), Day -1 
(Cohorts 1 through 3 only), Day 1 (30 minutes prior to the initiation of the study drug 
infusion, and at 0.5, 0.75, 1, 2, 4, 8 hours after initiation of the study drug infusion), Day 2 
(at 24, 30, and 36 hours after initiation of the study drug infusion), Day 3 (at 42 and 48 
hours after the initiation of the study drug infusion), Day 4, Day 7, Day 28/EOS. Vital sign 


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measurements will include systolic and diastolic blood pressures, oral body temperature, 
respiratory rate, and heart rate.  
During the initial 30 minutes of study drug infusion, systolic and diastolic blood pressures 
and heart rate will be collected every 5 minutes. 
Vital signs results will be presented in a data listing sorted by treatment group, subject, and 
collection date/time. Actual results and change from baseline will be summarized for the 
safety population.  
8.4. Twelve-Lead Electrocardiogram and Telemetry Monitoring 
Triplicate 12-lead ECGs will be obtained after the subject has been in the supine position 
for at least 10 minutes at Screening, within 1 hour prior to the initiation of the study drug 
infusion, and at 1 hour, 4 hours, 5 hours, 24 hours, and 48 hours after the initiation of the 
study drug infusion, and on Day 7 and Day 28/EOS and as indicated by AEs or telemetry 
findings. Electrocardiogram assessments will include comments on whether the tracings 
are normal or abnormal, rhythm, presence of arrhythmia or conduction defects, 
morphology, any evidence of myocardial infarction, or ST-segment, T-Wave, and U-Wave 
abnormalities. In addition, measurements of the following intervals will be measured and 
reported: RR interval, PR interval, QRS width, and Fridericia-corrected QT interval 
(QTcF). The investigator will determine whether any of the 12-lead ECG results are 
clinically significant or not.  
If both QT and RR intervals are not missing, the Bazett’s-corrected QT interval (QTcB) 
measured in msec will be calculated using below formula, where RR interval is measured 
in msec: 
• ܳܶܥܤ=
ொ்
ඥோோ/ଵ଴଴଴ 
If both QT and RR intervals are not missing but QTcF interval is missing in the database, 
QTcF measured in msec will be calculated using below formula, where RR interval is 
measured in msec: 


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• ܳܶܥܨ=
ொ்
ඥோோ/ଵ଴଴଴
య
 
Electrocardiogram results will be presented in data listing sorted by treatment group, 
subject, and date/time of assessment. In addition, subjects with outlying QTcF, and QTcB 
intervals (absolute value > 500 msec, absolute value > 480 msec, absolute value > 450 
msec, or increase from baseline value >30 or >60 msec) will be listed in a separate data 
listing based on the International Council for Harmonisation (ICH) harmonized tripartite 
guideline E14. A summary table will be presented for maximum QTcF and QTcB intervals 
(including scheduled and unscheduled assessments) meet the outlying criteria using count 
and percentage. 
Actual results and change from baseline will be summarized for the safety population 
using the average values of the triplicate ECG assessments at each timepoint. Baseline is 
defined as the last non-missing average value prior to the first study drug administration. 
Cardiac telemetry will be collected starting on Day -1 approximately 12 hours prior to the 
initiation of the study drug infusion (Hour 0) and will continue until subject is discharged 
from the clinical site for Cohorts 1-9. Cohort 10 subjects will discontinue cardiac telemetry 
monitoring on Day 3. For Cohorts 4-10, cardiac telemetry monitoring will begin on Day -3 
(check in) approximately 12 hours prior to the first dose of Ticagrelor and will be removed 
once dosed with Ticagrelor. Telemetry assessment results will be listed. 
8.5. Physical Examination and Physical Measurements 
Full physical examination (including height, weight, and BMI calculation, assessment of 
skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, abdomen, 
lymph nodes, and musculoskeletal system/extremities) will be performed at screening and 
Day 28 only. Brief physical examinations will include assessment of skin (including any 
signs for cutaneous erythema), lungs, cardiovascular system, and abdomen (liver, spleen) 
and will be performed at Day -3 (Cohorts 4 through 10 only), Day -1 (Cohorts 1 through 3 
only), Day 3, and Day 7.  


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Interim physical examinations will be performed at the discretion of the investigator, if 
necessary, to evaluate AEs or clinical laboratory abnormalities. 
Physical examination data will be listed. Screening height, weight and BMI will be 
summarized together with demographics variables.  
9. Immunogenicity Analysis 
Immunogenicity (antibody) samples will be screened for the presence of binding anti-drug 
antibody (ADA) on Day -3 (Cohorts 4 through 10 only), Day -1 (Cohorts 1 through 3 
only), Day 7, and Day 28/EOS. A subject testing positive for ADA at the final planned 
visit (Day 28) will be asked to return for follow-up sampling approximately 3 months after 
their final visit and approximately every 6 months thereafter until these no longer test 
positive or until levels return to a pre-dose state. 
The ADA result (positive or negative) will be summarized by treatment group and visit 
using counts and percentages. All ADA results with corresponding titer values will be 
presented in a data listing. The neutralizing antibody (NAb) results may be listed and 
summarized in the clinical study report if the assay is available. 
10. Pharmacokinetic Analysis 
The PK population will be used for all PK analysis tables and figures. 
10.1. 
Plasma Pharmacokinetics 
10.1.1. Plasma Pharmacokinetics Concentration 
Blood samples for PK analysis of total and unbound PB2452 concentration in plasma will 
be collected from all subjects at the following time points: before dosing (0 hour) and up to 
28 days after initiation of the study drug (PB2452 or placebo) infusion. Since ticagrelor is 
not administered to cohort 1-3 subjects, only unbound PB2452 concentration data will be 
collected for cohort 1-3 subjects.  Specific collection times for each cohort relative to the 
initiation of the study drug (PB2452 or placebo) infusion on Day 1 are listed in the table 
below: 


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Summary of Pharmacokinetic Assessments for PB2452 
Cohorts 1-6 -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours, and 7 and 28 
days  
Cohorts 7-8 -10 minutes 5 minutes and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 8.25, 8.5, 9, 10, 11, 12, 
16, 20, 24, 32, and 48 hours, and 7 and 28 days  
Cohorts 9-10 -10 minutes, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 
32, 36, 48 hours, 7 and 28 days 
 
Plasma samples for determining total and unbound concentrations of ticagrelor and its active 
metabolite AR-C124910XX, will be collected from subjects in Cohorts 4 through 10 at the 
following timepoints: before dosing (within 10 minutes prior to the initiation of the study 
drug infusion [Hour 0]), and up to 48 hours following the initiation of study drug infusion 
on Day 1. Of note, subjects in Cohorts 4-6 will be administered the 5th ticagrelor dose and 
study drug infusion simultaneously, whereas subjects in Cohorts 7-10 will be administered 
the 5th ticagrelor dose two hours before the study drug infusion initiation on Day 1. 
Specific collection times for each cohort relative to the initiation of the study drug (PB2452 
or placebo) infusion are listed in the table below: 
Summary of Pharmacokinetic Assessments for Ticagrelor and Active Metabolite AR-
C124910XX 
Cohorts 4-6 -10 minutes and 0.5, 1, 2, 3, 6, 12, 24 and 48 hours  
Cohorts 7-8 -10 minutes, 5 minutes and 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 14, 16, 20, 24, 32 
and 48 hours  
Cohorts 9-10 -10 minutes, 5 minutes, 0.25, 0.5, 1, 2, 3, 6, 8, 12, 14, 16, 20, 24, 28, 36 and 
48 hours 
 


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Concentrations that are below the limit of quantification (BLQ) will be treated as zero for 
descriptive statistics. Mean BLQ concentrations will be presented as BLQ, and the SD and 
coefficient of variation (CV) will be reported as not applicable. Missing concentrations 
will be excluded from the calculations. 
For each analyte, plasma concentration data will be listed by subject and summarized by 
time point for each dose level using descriptive statistics (number of subjects, mean, SD, 
CV, median, minimum, and maximum).  Plasma concentration versus time profiles for 
each subject will be presented graphically. The mean plasma concentrations versus 
scheduled time profiles by dose will be presented graphically. 
Scatter plots of total and unbound plasma ticagrelor and AR-C124910XX versus total and 
unbound PB2452 plasma concentration will be prepared for all cohorts, as appropriate.  
10.1.2. Plasma Pharmacokinetic Parameters 
The PK parameters of PB2452, ticagrelor, and AR-C124910XX will be determined using 
noncompartmental methods using Phoenix WinNonlin Version 6.4 or higher or SAS® 
Version 9.3 or higher. For PK analysis, BLQ values will be treated as zero with the 
exception that a BLQ value between 2 quantifiable concentrations will be set as missing. If 
consecutive BLQ concentrations are followed by quantifiable concentrations in the 
terminal phase, those concentrations after BLQ concentrations will be treated as missing. 
Missing concentrations will be treated as missing from the PK parameter calculations. 
The following PK parameters, if data permits, will be calculated for total and unbound 
plasma PB2452 using actual sampling times. 
PB2452 PK parameters: 
Parameter 
Description 
Cmax 
Observed maximum plasma concentration 
Tmax 
Time to reach the observed maximum plasma concentration 


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AUC0-t 
Area under the plasma concentration versus time curve (AUC) from time 
0 to the time of last quantifiable concentration (Clast); calculated using 
the linear-up/ log-down trapezoidal rule 
AUC0-inf 
AUC from time 0 extrapolated to infinity, calculated as AUC0-t + Clast/ 
λz, where Clast is the last quantifiable plasma drug concentration and λz 
is the terminal phase rate constant. 
AUC0-48 
AUC from time 0 to 48 hours post-dose; calculated using the linear-up/ 
log-down trapezoidal rule  
%AUCextrap Percentage of AUC0-inf due to extrapolation from the time for the last 
quantifiable concentration to infinity, calculated as (AUC0-inf -
AUC0-t)/AUC0-inf*100 
λz  
Terminal phase rate constant, determined by linear regression of the 
terminal points of the log-linear plasma concentration-time curve. The λz 
will not be estimated if the terminal phase of the log-concentration-time 
profile does not exhibit a linear decline phase, or if the regression 
coefficient (Rsq) is less than 0.8. 
Rsq 
Regression coefficient for calculation of λz 
t1/2 
Terminal elimination half-life, calculated as t1/2= ln(2)/ λz. 
CL 
Total body clearance, calculated as Dose/AUC0-inf 
Vd 
Volume of distribution, calculated as CL/λz. 
 
The following PK parameters, as appropriate and when data permit, will be calculated for 
ticagrelor and AR-C124910XX (total and unbound plasma) using actual sampling times: 


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Ticagrelor/ AR-C124910XX PK parameters: 
Parameter 
Description 
Cmax 
Observed maximum plasma concentration 
Tmax 
Time to reach the observed maximum plasma concentration 
AUC0-t 
AUC from time 0 to the time of last quantifiable concentration (Clast); 
calculated using the linear-up/ log-down trapezoidal rule 
AUC0-inf 
AUC from time 0 extrapolated to infinity, calculated as AUC0-t + Clast/ 
λz, where Clast is the last quantifiable plasma drug concentration and λz 
is the terminal phase rate constant. 
AUC0-48 
AUC from time 0 to 48 hours post-dose; calculated using the linear-up/ 
log-down trapezoidal rule 
%AUCextrap Percentage of AUC0-inf due to extrapolation from the time for the last 
quantifiable concentration to infinity, calculated as (AUC0-inf -
AUC0-t)/AUC0-inf*100 
λz  
Terminal phase rate constant, determined by linear regression of the 
terminal points of the log-linear plasma concentration-time curve. The λz 
will not be estimated if the terminal phase of the log-concentration-time 
profile does not exhibit a linear decline phase, or if the regression 
coefficient (Rsq) is less than 0.8. 
Rsq 
Regression coefficient for calculation of λz 
t1/2 
Terminal elimination half-life, calculated as t1/2= ln(2)/ λz. 
 


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Additional PK parameters may be calculated, as necessary. Pharmacokinetic parameters 
will be listed by subject and summarized for each dose level using descriptive statistics 
(number of subjects, mean, SD, CV, median, minimum, and maximum), with the exception 
of %AUCextrap, λz and Rsq, which will be listed only. Geometric means will be reported 
for AUCs and Cmax. 
10.1.3. Plasma Pharmacokinetic Parameters Analysis 
Dose proportionality will be tested using the power regression model for AUC0-inf, AUC0-t, 
and Cmax of total and unbound PB2452 in Cohorts 4, 5, and 6.  
A power model will be fit to describe the relationship between Y (Cmax, AUC0-t, and 
AUC0-∞) and X (dose) using the least-squares linear regression model [ln(Y) = ln(α) + β 
ln(X), which is the logarithmic form of Y = αXβ]. From each model, the intercept of 
regression line [ln(α)] and the slope of the regression line β will be presented along with 
the 90% confidence interval (CI) of the slope. This model will be fit for total and unbound 
PB2452 in Cohorts 4, 5, and 6. The dose proportionality will be declared when the 90% CI 
for β lies entirely within the critical region, 
 
൬1 + ln(0.5)
ln(ݎ) , 1 + ln(2.0)
ln(ݎ)   ൰ 
where r is the ratio of the highest and the lowest dose included in the power model. 
10.2. 
Urine Pharmacokinetics 
10.2.1. Urine pharmacokinetic Concentrations 
Pooled urine samples to assess urine ticagrelor and AR-C124910XX concentrations will be 
collected from subjects in Cohorts 4 through 10 over the following intervals: before dosing 
(within 60 minutes prior to the first ticagrelor dose on Day -2) and 0 to 6, 6 to 12, 12 to 24, 
and 24 to 48 hours after the initiation of the study drug infusion. 
Urine concentration data will be listed by collection interval for each subject. 


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10.2.2. Urine Parameters 
The following PK parameters for ticagrelor and AR-C124910XX concentrations in urine 
will be calculated whenever data permits: 
 
Parameter Description 
Ae48 
Total amount of drug excreted in urine from time 0 to 48 hours   
Aet1-t2 
Ae from time t1 to t2 hours where the values of t1 to t2 are 0 to 6, 6 to 12, 
12 to 24, and 24 to 48 
Fe48 
Fraction excreted in urine from 0 to 48 hours after dosing  
CLr48 
Renal clearance, calculated as Ae48/AUC0-48  
 
Additional urine PK parameters may be calculated, as necessary. Urine parameters will be 
listed by subject and summarized for each dose level using descriptive statistics (number of 
subjects, mean, SD, CV, median, minimum, and maximum). 
11. Pharmacodynamic Analysis 
The PD population will be used for all PD analysis tables and figures, except otherwise 
noted. 
11.1. 
 Pharmacodynamic Data 
Blood samples for PD analysis will be collected from subjects in Cohorts 4 through 10 at the 
following time points: before dosing (within 60 minutes prior to 1st ticagrelor dose on Day -2) 
and again before dosing (within 10 minutes prior to the initiation of the study drug infusion 
[Hour 0]), and up to 48 hours after the initiation of study drug infusion. Specific collection 
times are listed in the table below: 


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Summary of Pharmacodynamic Assessments 
Cohorts 4-6 
Day -2 (60 minutes prior to 1st ticagrelor dose) and Day 1 (-10 minutes, 
0.5, 1, 2, 3, 6, 12, 24 and 48 hours)  
Cohorts 7-8 
Day -2 (60 minutes prior to first 1st dose) and Day 1 (-10 minutes, 5 
minutes and 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 16, 20, 24 and 48 hours) 
Cohort 9-10 
Day -2 (60 minutes prior to first ticagrelor dose) and Day 1 (-10
minutes, 5 minutes, 0.25, 0.5, 1, 2, 3, 6, 8, 12, 16, 20, 24, 28, 36 and 48 
hours) 
 
Platelet aggregation will be assessed using the LTA, VerifyNow, and VASP assays. The 
results of platelet aggregation from the LTA assay (using 5µM ADP and 20µM ADP) will 
be expressed as maximal-extent aggregation (MA), %baseline MA, final-extent 
aggregation (FA) and %baseline FA, which will be calculated from the platelet 
aggregation-time profile for each sampling time point. The results for the VerifyNow assay 
will be expressed as PRU and %baseline PRU, which will be calculated from the platelet 
aggregation-time profile for each sampling time point. Similarly, PD results from the 
VASP assay will be expressed as PRI and %baseline PRI, which will be calculated from 
the platelet aggregation-time profile for each sampling time point. PD data will be listed by 
subject with ADA status and summarized for each treatment group for each time point 
using descriptive statistics (number of subjects, mean, SD, median, minimum, and 
maximum). A ADA-positive subject is defined as a subject with at least one ADA-positive 
sample at any time during the treatment or follow-up observation period. In case of a 
positive pre-treatment sample, if the titer of at least one post-treatment ADA is elevated at 
least 2 folds of the titer in pre-treatment sample, this subject is also ADA positive 
otherwise ADA negative. 
Mean PD data versus scheduled time profiles will be presented graphically.  


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Scatter plots of PD data versus total and unbound PB2452 plasma concentrations will be 
prepared for all cohorts, as appropriate. A box plot of PD data versus sampling time point 
will be prepared for each dose level.  
Correlation between LTA assay, VerifyNow assay and VASP assay will be investigated 
graphically. Scatter plots of individual subject MA versus PRU (5µM ADP and 20µM 
ADP), MA versus PRI (5µM ADP and 20µM ADP), and PRU versus PRI will be plotted, 
and the correlation coefficient r (Spearman's rank correlation coefficient) and p-value will 
be displayed. 
11.2. 
 Pharmacodynamic Parameters 
Pharmacodynamic parameters will be calculated using actual timepoints using SAS® 
Version 9.3 or higher. Missing PD values will be treated as missing for PD parameter 
calculation.  
The following PD parameters will be calculated using %baseline/actual MA and FA data, 
as appropriate, from the LTA assay for both the 5µM and 20µM ADP conditions.  
 
Parameters following study drug infusion: 
APAmax 
Maximal actual platelet aggregation 
PAmax 
Maximal percent of baseline platelet aggregation 
TPAmax 
Time to maximal actual platelet aggregation 
TPA60% 
Time to 60% of baseline platelet aggregation, calculated as the first time 
point when %baseline platelet aggregation reaches 60% or above. 
TPA80% 
Time to 80% of baseline platelet aggregation, calculated as the first time 
point when %baseline platelet aggregation reaches 80% or above 
TPA90% 
Time to 90% of baseline platelet aggregation, calculated as the first time 
point when %baseline platelet aggregation reaches 90% or above 
 
The following PD parameters will be calculated using %baseline/actual PRU data from the 
VerifyNow assay. 


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Parameters following study drug infusion: 
PRUmax 
Maximal actual PRU 
TPRUmax 
Time to maximal actual PRU 
TPRU200 
Time to 200 or higher PRU, calculated as the first time point when the 
actual PRU reaches 200 or above 
TPRU60% 
Time to 60% of baseline PRU, calculated as the first time point 
when %baseline PRU reaches 60% or above 
TPRU80% 
Time to 80% of baseline PRU, calculated as the first time point 
when %baseline PRU reaches 80% or above 
TPRU90% 
Time to 90% of baseline PRU, calculated as the first time point 
when %baseline PRU reaches 90% or above 
 
The following PD parameters will be calculated using %baseline/actual PRI data from the 
VASP assay. 
Parameters following study drug infusion: 
APRImax 
Maximal actual PRI 
PRImax 
Maximal percent of baseline PRI 
TPRImax 
Time to maximal actual PRI 
TPRI60% 
Time to 60% of baseline PRI, calculated as the first time point 
when %baseline PRI reaches 60% or above 
TPRI80% 
Time to 80% of baseline PRI, calculated as the first time point 
when %baseline PRI reaches 80% or above 
TPRI90% 
Time to 90% of baseline PRI, calculated as the first time point 
when %baseline PRI reaches 90% or above 
 
Additional PD parameters may be calculated, as necessary. Pharmacodynamic parameters 
will be listed by subject and summarized for each cohort using descriptive statistics 
(number of subjects, mean, SD, median, minimum, and maximum). 


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12. Changes in the Planned Analysis 
For ECG measurements, QTcB interval will be calculated and a summary table for QTcF 
and QTcB values outside of pre-defined criteria will be produced. 
13. Interim Analysis 
There’s no planned formal interim analysis for this study. Blinded safety data review for 
each dose cohort will be performed before dosing in the next cohort is allowed 
(Section 3.4.2.1 of the protocol). 
Interim noncompartmental analyses of PK data and/or PK/PD modeling will be performed 
as needed. 
 


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14. Reference 
Memo Re: PB2452-PT-CL-0001 Cohort 7 Dosing Regimen. To: Lu Ann Bundrant, MD, 
Principal Investigator, PPD Early Development Services; Tiffany Reyes, Associate Director, 
Project Management, PPD Early Development. CC: Casey Davis, Project Manager, PPD 
Early Development. From: JoAnn Malatesta, Director, Clinical Operations. Date: July 3, 
2018. 
Memo Re: PB2452-PT-CL-0001 Cohort 8 Dosing Regimen. To: Lu Ann Bundrant, MD, 
Principal Investigator, PPD Early Development Services; Tiffany Reyes, Associate Director, 
Project Management, PPD Early Development. CC: Casey Davis, Project Manager, PPD 
Early Development. From: JoAnn Malatesta, Director, Clinical Operations. Date: July 25, 
2018. 
Memo Re: PB2452-PT-CL-0001 Cohort9 and 10 Dosing Regimens. To: Lu Ann Bundrant, 
MD, Principal Investigator, PPD Early Development Services; Tiffany Reyes, Associate 
Director, Project Management, PPD Early Development. CC: Casey Davis, Project Manager, 
PPD Early Development. From: Janet Rush, MD, Sponsor Medical Consultant. Date: August 
8, 2018. 


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15. Table of Contents: Tables, Listings and Figures 
 
List of Tables 
 
Subject Disposition 
Table 14.1.1. 
Subject Disposition 
 
Demographics and Baseline Characteristics 
Table 14.1.2  
Demographic and Baseline Characteristics (Safety Population) 
 
Pharmacokinetics 
Table 14.2.1.1 
Summary of Total Plasma PB2452 Concentrations (unit) (PK 
Population) 
Table 14.2.1.2 
Summary of Unbound Plasma PB2452 Concentrations (unit) 
(PK Population) 
Table 14.2.1.3 
Summary of Total Plasma Ticagrelor and AR-C124910XX 
Concentrations (unit) (PK Population) 
Table 14.2.1.4 
Summary of Unbound Plasma Ticagrelor and AR-C124910XX 
Concentrations (unit) (PK Population) 
Table 14.2.2.1 
Summary of Total Plasma Pharmacokinetic Parameters of 
PB2452 (PK Population) 
Table 14.2.2.2 
Summary of Unbound Plasma Pharmacokinetic Parameters of 
PB2452 (PK Population) 
Table 14.2.2.3 
Summary of Total Plasma Pharmacokinetic Parameters of 
Ticagrelor and AR-C124910XX (PK Population) 
Table 14.2.2.4 
Summary of Unbound Plasma Pharmacokinetic Parameters of 
Ticagrelor and AR-C124910XX (PK Population) 
Table 14.2.3.1 
 
Statistical Assessment of Dose Proportionality for Total Plasma 
PB2452: Cohorts 4 to 6 (PK Population) 
Table 14.2.3.2 
 
Statistical Assessment of Dose Proportionality for Unbound 
Plasma PB2452: Cohorts 4 to 6 (PK Population) 


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Table 14.2.4.1 
Summary of Urine Pharmacokinetic Parameters of Ticagrelor 
and AR-C124910XX (PK Population) 
Pharmacodynamics 
 
Table 14.2.5.1 
Summary of Platelet Aggregation Results from LTA Assay 
(Safety Population) 
Table 14.2.5.2 
Summary of PRU Results from VerifyNow Assay 
(Safety Population) 
Table 14.2.5.3 
 
Summary of PRI Results from VASP Assay (Safety 
Population) 
Table 14.2.6.1 
Summary of Pharmacodynamic Parameters for LTA Assay (PD 
Population) 
Table 14.2.6.2 
Summary of Pharmacodynamic Parameters for VerifyNow 
Assay (PD Population) 
Table 14.2.6.3 
Summary of Pharmacodynamic Parameters for VASP Assay 
(PD Population) 
Safety 
Table 14.3.1.1 
Overall Summary of Adverse Events (Safety Population) 
Table 14.3.1.2 
Treatment-emergent Adverse Events (TEAEs) by System 
Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.3 
Treatment-emergent Adverse Events (TEAEs) by Preferred 
Term (Safety Population) 
Table 14.3.1.4 
Treatment-emergent Adverse Events (TEAEs) by System 
Organ Class, Preferred Term and Relationship to the Study 
Drug (Safety Population) 
Table 14.3.1.5 
Treatment-emergent Adverse Events (TEAEs) by System 
Organ Class, Preferred Term, and Relationship to Ticagrelor 
(Safety Population) 


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Table 14.3.1.6 
Treatment-emergent Adverse Events (TEAEs) by System 
Organ Class, Preferred Term, and Severity (Safety Population) 
Table 14.3.2.1 
Listing of Serious Adverse Events (Safety Population) 
Table 14.3.2.2 
Listing of Adverse Events Leading to Early Discontinuation 
(Safety Population) 
Table 14.3.4.1.1 
Actual Values and Changes from Baseline in Hematology and 
Coagulation (Safety Population) 
Table 14.3.4.1.2 
Actual Values and Changes from Baseline in Serum Chemistry 
(Safety Population) 
Table 14.3.4.1.3 
Actual Values and Changes from Baseline in Urinalysis (Safety 
Population) 
Table 14.3.4.2.1 
Shifts from Baseline in Hematology and Coagulation (Safety 
Population) 
Table 14.3.4.2.2 
Shifts from Baseline in Serum Chemistry (Safety Population) 
Table 14.3.4.2.3 
Shifts from Baseline in Urinalysis (Safety Population) 
Table 14.3.5.1 
Actual Values and Changes from Baseline in Vital Sign 
Measurements (Safety Population) 
Table 14.3.6.1 
 
Actual Values and Changes from Baseline in 12-Lead 
Electrocardiograms (Safety Population) 
Table 14.3.6.2 
Summary of Subjects with QTc Intervals Out of Pre-Defined 
Criteria (Safety Population) 
Table 14.3.7 
Immunogenicity (Safety Population) 
List of Listings 
 
Subject Disposition 
Listing 16.1.7 
Randomization (Randomized Population) 
Listing 16.2.1.1 
Screen Failures 
Listing 16.2.1.2 
Subject Disposition (Randomized Population) 


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Listing 16.2.2.1 
Protocol Deviations (Randomized Population) 
Listing 16.2.2.2 
Eligibility (Randomized Population) 
 
Demographic and Baseline Characteristics 
Listing 16.2.4.1 
Demographic and Baseline Characteristics (Randomized 
Population) 
Listing 16.2.4.2 
Medical History (Randomized Population) 
 
 
Treatment and Medications 
Listing 16.2.4.3 
Medical or Surgical Treatment Procedures (Randomized 
Population) 
Listing 16.2.4.4 
Prior and Concomitant Medications (Randomized Population) 
Listing 16.2.5.1 
PB2452 or Placebo Administration – Cohorts 1 to 6 (Safety 
Population) 
Listing 16.2.5.2 
PB2452 or Placebo Administration – Cohorts 7 to 10 (Safety 
Population) 
Listing 16.2.5.3 
Ticagrelor Administration (Safety Population) 
 
 
Pharmacokinetics 
 
Listing 16.2.6.1.1 
Total and Unbound Plasma PB2452 Concentrations (Safety 
Population) 
Listing 16.2.6.1.2 
Total Plasma Ticagrelor and AR-C124910XX Concentrations 
(Safety Population) 
Listing 16.2.6.1.3 
Unbound Plasma Ticagrelor and AR-C124910XX 
Concentrations (Safety Population) 
Listing 16.2.6.2.1 
Total and Unbound Plasma Pharmacokinetic Parameters of 
PB2452 (PK Population) 


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Listing 16.2.6.2.2 
Total and Unbound Plasma Pharmacokinetic Parameters of 
Ticagrelor and AR-C124910XX (PK Population) 
Listing 16.2.6.3.1 
Urine Concentrations of Ticagrelor and AR-C124910XX and 
Urine Volumes (Safety Population) 
Listing 16.2.6.3.2 
Urine Pharmacokinetic Parameters for Ticagrelor and AR-
C124910XX (Safety Population) 
Pharmacodynamics 
 
Listing 16.2.6.4.1 
Pharmacodynamic Results from LTA Assay (Safety Population) 
Listing 16.2.6.4.2 
Pharmacodynamic Results from VerifyNow Assay (Safety 
Population) 
Listing 16.2.6.4.3 
Pharmacodynamic Results from VASP Assay (Safety 
Population) 
Listing 16.2.6.5.1 
Pharmacodynamic Parameters from LTA Assay (PD Population) 
Listing 16.2.6.5.2 
 
Pharmacodynamic Parameters from VerifyNow Assay (PD 
Population) 
Listing 16.2.6.5.3 
 
Pharmacodynamic Parameters from VASP Assay (PD 
Population) 
Safety and Immunogenicity 
Listing 16.2.7.1 
Adverse Events (Safety Population) 
Listing 16.2.8.1 
Hematology and Coagulation Laboratory Test Results (Safety 
Population) 
Listing 16.2.8.2 
Serum Chemistry Laboratory Test Results (Safety Population) 
Listing 16.2.8.3 
Urinalysis Laboratory Test Results (Safety Population) 
Listing 16.2.8.4 
Other Laboratory Test Results (Safety Population) 
Listing 16.2.9.1 
Vital Sign Measurements (Safety Population) 
Listing 16.2.9.2 
Physical Measurements (Safety Population) 
Listing 16.2.9.3 
12-Lead Electrocardiograms (Safety Population) 


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Listing 16.2.9.4 
Subjects with QTc Intervals Out of Pre-Defined Criteria (Safety 
Population) 
Listing 16.2.9.5 
Telemetry Monitoring (Safety Population) 
Listing 16.2.9.6 
Physical Examinations (Safety Population) 
Listing 16.2.9.7 
Immunogenicity (Safety Population) 
List of Figures 
 
Pharmacokinetics 
 
Figure 14.2.1.1 
Mean (+/- SD) Total Plasma Concentration versus Time Profiles 
for PB2452 (PK Population) 
Figure 14.2.1.2 
Mean (+/- SD) Unbound Plasma Concentration versus Time 
Profiles for PB2452 (PK Population) 
Figure 14.2.1.3 
Mean (+/- SD) Total Plasma Concentration versus Time Profiles 
for Ticagrelor and AR-C124910XX (PK Population) 
Figure 14.2.1.4 
Mean (+/- SD) Unbound Plasma Concentration versus Time 
Profiles for Ticagrelor and AR-C124910XX 
(PK Population) 
Figure 14.2.2.1 
Individual Total Plasma Concentration versus Time Profiles for 
PB2452 (Safety Population) 
Figure 14.2.2.2 
Individual Unbound Plasma Concentration versus Time Profiles 
for PB2452 (Safety Population) 
Figure 14.2.2.3 
Individual Total Plasma Concentration versus Time Profiles for 
Ticagrelor and AR-C124910XX (Safety Population) 
Figure 14.2.2.4 
Individual Unbound Plasma Concentration versus Time Profiles 
for Ticagrelor and AR-C124910XX (Safety Population) 
Figure 14.2.3.1 
Scatterplot of Total Plasma Ticagrelor and AR-C124910XX vs 
Total Plasma PB2452 Concentration (PK Population) 


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Figure 14.2.3.2 
Scatterplot of Total Plasma Ticagrelor and AR-C124910XX vs 
Unbound Plasma PB2452 Concentration (PK Population) 
Figure 14.2.3.3 
Scatterplot of Unbound Plasma Ticagrelor and AR-C124910XX 
vs Total Plasma PB2452 Concentration (PK Population) 
Figure 14.2.3.4 
Scatterplot of Unbound Plasma Ticagrelor and AR-C124910XX 
vs Unbound Plasma PB2452 Concentration (PK Population) 
Pharmacodynamics 
Figure 14.2.4.1 
Mean (+/- SD) %Baseline Platelet Aggregation versus Time 
Profiles from LTA Assay using 5µM ADP 
 (PD Population) 
Figure 14.2.4.2 
Mean (+/- SD) %Baseline Platelet Aggregation versus Time 
Profiles from LTA Assay using 20µM ADP (PD Population) 
Figure 14.2.4.3 
Mean (+/- SD) PRU versus Time Profiles from VerifyNow 
Assay (PD Population) 
Figure 14.2.4.4 
Mean (+/- SD) %Baseline PRI versus Time Profiles from VASP 
Assay (PD Population) 
Figure 14.2.5.1 
Individual %Baseline Platelet Aggregation Results versus Time 
Profiles from LTA Assay using 5µM ADP  
(Safety Population)  
Figure 14.2.5.2 
Individual %Baseline Platelet Aggregation Results versus Time 
Profiles from LTA Assay using 20µM ADP  
(Safety Population) 
Figure 14.2.5.3 
Individual PRU Results versus Time Profiles from VerifyNow 
Assay (Safety Population) 
Figure 14.2.5.4 
Individual %Baseline PRI Results versus Time Profiles from 
VASP Assay (Safety Population) 


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Figure 14.2.6.1 
Scatter Plot of Platelet Aggregation Results from LTA Assay 
using 5µM ADP versus Total Plasma PB2452 Concentration (PD 
Population) 
Figure 14.2.6.2 
Scatter Plot of Platelet Aggregation Results from LTA Assay 
using 5µM ADP versus Unbound Plasma PB2452 Concentration 
(PD Population) 
Figure 14.2.6.3 
Scatter Plot of Platelet Aggregation Results from LTA Assay 
using 20µM ADP versus Total Plasma PB2452 Concentration 
(PD Population) 
Figure 14.2.6.4 
Scatter Plot of Platelet Aggregation Results from LTA Assay 
using 20µM ADP versus Unbound Plasma PB2452 
Concentration (PD Population) 
Figure 14.2.6.5 
Scatter Plot of PRU Results from VerifyNow versus Total 
Plasma PB2452 Concentration (PD Population) 
Figure 14.2.6.6 
Scatter Plot of PRU Results from VerifyNow versus Unbound 
Plasma PB2452 Concentration (PD Population) 
Figure 14.2.6.7 
Scatter Plot of PRI Results from VASP versus Total Plasma 
PB2452 Concentration (PD Population) 
Figure 14.2.6.8 
Scatter Plot of PRI Results from VASP versus Unbound Plasma 
PB2452 Concentration (PD Population) 
Figure 14.2.7.1 
Box Plot of Platelet Aggregation from LTA Assay using 5µM 
ADP versus Time by Cohort (Safety Population) 
Figure 14.2.7.2 
Box Plot of Platelet Aggregation from LTA Assay using 20µM 
ADP versus time by Cohort (PD Population)  
Figure 14.2.7.3 
 
Box Plot of PRU Results from VerifyNow versus time by Cohort 
(PD Population) 
Figure 14.2.7.4 
 
Box Plot of PRI Results from VASP versus time by Cohort (PD 
Population)  


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Figure 14.2.8.1 
 
Scatter Plot of LTA (5µM ADP) vs VerifyNow PD Data at 
Baseline or post-Baseline (Safety Population)  
Figure 14.2.8.2 
Scatter Plot of LTA (20µM ADP) vs VerifyNow PD Data 
(Safety Population) 
Figure 14.2.8.3 
 
Scatter Plot of LTA (5µM ADP) vs VASP PD Data (Safety 
Population)  
Figure 14.2.8.4 
 
Scatter Plot of LTA (20µM ADP) vs VASP PD Data (Safety 
Population)  
Figure 14.2.8.5 
 
Scatter Plot of VerifyNow vs VASP PD Data (Safety 
Population)