Clinical trial NCT05093790
Conditions: Coronary Artery Disease Healthy Participants
Keywords: Thrombosis Coronary Artery Disease Healthy Participants Aspirin Ticagrelor Brilinta BMS-986141
Sponsor: Bristol-Myers Squibb
Start date: 2022-03-25; Completion date: 2022-11-14
Enrollment: 58 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the effectiveness, safety and tolerability of BMS-986141 added on to aspirin or ticagrelor or the combination on thrombus formation in both healthy participants and participants with stable coronary artery disease.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None arm 4: None
Interventions: intervention 1: Ticagrelor intervention 2: BMS-986141 intervention 3: Aspirin
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days intervention 3: Specified dose on specified days

Protocol documents:
Prot_SAP_000.pdf: 
Page:
1
Protocol Number:
CV006037
Date:
05-Jan-2021
Revised Date:
17-Sep-2021 
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND: N/A
EudraCT: 2020-005209-18
NCT: N/A
WHO: N/A
EUDAMED: N/A
Other: N/A
CLINICAL PROTOCOL CV006037
A Phase 2a Single Dose Study to Evaluate the Effect of BMS-986141 Added on to Aspirin or 
Ticagrelor or the Combination, on Thrombus Formation in an Ex Vivo Thrombosis Chamber 
Model in Patients With Stable Coronary Artery Disease and Healthy Participants
Short Title:
A Phase 2a Single Dose Study to Evaluate BMS-986141 Added on to Aspirin or Ticagrelor or the 
Combination, on Thrombus Formation in a Thrombosis Chamber Model in Patients and Healthy 
Participants
Protocol Amendment 02
Study Director/Medical Monitor
Medical Monitor
3401 Princeton Pike
Lawrenceville, NJ 08648
3900 Paramount Parkway
Morrisville, NC 27560
Telephone (office): 
Telephone (24/7): 
Fax: 
24-hr Emergency Telephone Number
USA: 
International: 
Bristol-Myers Squibb Company
3401 Princeton Pike
Lawrenceville, NJ 08648
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
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Protocol Amendment No.: 02
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confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).
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Protocol Amendment No.: 02
Date: 17-Sep-2021
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol Amendment 02
17-Sep-2021
Modifications 
 to 
clarify treatment allocation, returning to previous therapy, 
contraception, stopping rules, and add the exclusion of 
patients with contraindications to study drugs.
Protocol Amendment 01
18-Mar-2021
Changed dose and dose formulation to 4 mg oral tablet.
Original Protocol
05-Jan-2021
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02:
The purpose of this protocol amendment is to apply changes 
 
 Modifications 
 
 have been applied to clarify treatment allocation, returning to previous 
therapy, contraception, stopping rules, and add the exclusion of patients with contraindications to 
study drugs. Clarifications to reflect these revisions were made throughout the protocol 
amendment to maintain consistency. 
This protocol amendment will be implemented after the investigator receives all appropriate 
agency and Investigational Review Board/Ethics Committee approvals.
Generally, only major additions and deletions are provided in this summary document, and all 
minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes, are not included.
The rationale(s) for changes to this Protocol Amendment are provided in the summary of key 
changes table, as shown below:
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & 
Title
Description of Change
Brief Rationale
Table 2-2: On 
Treatment Procedural 
Outline (CV006037) -
Treatment Arms 1, 2, 
and 3
Table 2-3: On 
Treatment Procedural 
Outline (CV006037) -
Treatment Arm 4
Section 3.3: 
Benefit/Risk 
Assessment
Section 7.9: Return to 
Previous Therapy
Added information for participants who 
will be returning to previous therapy 
following the study.
Added reference to new Section 7.9: 
return to previous therapy.
Added section to provide guidance for 
the return to previous therapy upon 
completion of study therapy.
added
guidance for return to previous therapies.
Table 2-2: On 
Treatment Procedural 
Outline (CV006037) -
Treatment Arms 1, 2, 
and 3
Table 2-3: On 
Treatment Procedural 
Outline (CV006037) -
Treatment Arm 4
9.4.1.1: Medical 
Photography
The term ‘rash’ has been removed and 
replaced with ‘clinical findings’ to 
allow for photos of any change may be 
taken. Instruction to determine 
necessity of photographs is at the 
discretion of the principle investigator 
has been added.
To clarify any area affected by any clinical 
finding that can be captured by medical 
photography as per discretion by the 
Principal Investigator.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & 
Title
Description of Change
Brief Rationale
Section 5.1: Overall 
Design
Clarification of treatment allocation has 
been added.
 define method 
for allocation of participants to treatment 
arms.
Section 6.1: Inclusion 
Criteria
3)a)xi)2) Revised to further clarify type 
and duration of contraception for 
women of child bearing potential.
 duration of 
contraception requirements for WOCBP has 
been modified to align with Appendix 4.
Section 6.2: Exclusion 
Criteria
2)d) Added criteria for 
contraindications to any of the study 
drugs.
Exclusion 
Criteria for all contraindications to aspirin, 
ticagrelor as well as BMS-986141.
Section 6.4.1: Retesting 
During Screening or 
Lead-in Period
Section 7: Treatment
Section 9: Study 
Assessments and 
Procedures
Removed reference to participant 
randomization to clarify study 
participant allocation.
 define method 
for allocation of participants to treatment 
arms.
Section 7.7.1: 
Prohibited and/or 
Restricted Treatments
Revised #5 to clarify prohibited drugs 
within one week prior to study 
treatment
 define what 
concomitant medications are prohibited for 
the patient and healthy subject populations.
Section 7.2: Method of 
Treatment Assignment
Clarification of treatment allocation has 
been added with reference to Section 
5.1.
 define method 
for allocation of participants to treatment 
arms.
Section 8.1.2: Stopping 
Rules
Stopping rules revised to remove the 
requirement that the AE be the same.
Added sentence to clarify that dosing 
will not resume if any stopping rules 
are met.
Added sentence to clarify that to restart 
dosing after any stopping rules are met 
requires approval of a substantial 
amendment with justification.
 to clarify 
Stopping rule requirements.
Section 9.2.1: Time 
Period and Frequency 
for Collecting AE and 
SAE information
Updated the location of reference safety 
information.
 Safety 
Information RSI for Aspirin and Ticagrelor
are updated.
Appendix 4
Added sentence to further clarify type 
and duration of contraception for 
women of child bearing potential.
Less than highly effective contraceptive 
methods moved to unacceptable 
methods of contraception.
 duration of 
contraception requirements for WOCBP has 
been modified to align with Section 6.1: 
inclusion criteria..
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: ............................ 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 ................ 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 SYNOPSIS ................................................................................................................. 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.2.1 Nonclinical Pharmacology and Pharmacokinetics ................................. 
 
3.2.2 Nonclinical Toxicity ................................................................................. 
 
3.2.3 Clinical Pharmacology and Safety .......................................................... 
 
3.3 Benefit/Risk Assessment .................................................................................. 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Data Monitoring Committee and Other External Committees ................ 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.5 Justification for Dose ........................................................................................ 
 
6 STUDY POPULATION ............................................................................................ 
 
6.1 Inclusion Criteria .............................................................................................. 
 
6.2 Exclusion Criteria ............................................................................................. 
 
6.3 Lifestyle Restrictions ........................................................................................ 
 
6.3.1 Meals and Dietary Restrictions ............................................................... 
 
6.3.2 Caffeine, Alcohol and Tobacco ................................................................ 
 
6.3.3 Activity ..................................................................................................... 
 
6.4 Screen Failures .................................................................................................. 
 
6.4.1 Retesting During Screening or Lead-In Period ....................................... 
 
7 TREATMENT ........................................................................................................... 
 
7.1 Treatments Administered .................................................................................. 
 
7.2 Method of Treatment Assignment .................................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.5.1 Retained Samples for Bioavailability / Bioequivalence / Biocomparability
..................................................................................................................... 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
 
7.8 Treatment After the End of the Study ............................................................... 
 
7.9 Return to Previous Therapy .............................................................................. 
 
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8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation from Study Treatment ............................................................ 
 
8.1.1 Post Study Treatment Study Follow-up.................................................... 
 
8.1.2 Stopping Rules ......................................................................................... 
 
8.2 Discontinuation from the Study ........................................................................ 
 
8.3 Lost to Follow-Up ............................................................................................. 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
9.1.1 Imaging Assessment for the Study............................................................ 
 
9.2 Adverse Events ................................................................................................. 
 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
 
9.2.2 Method of Detecting AEs and SAEs ......................................................... 
 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
 
9.2.5 Pregnancy ................................................................................................ 
 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
 
9.2.7 Potential Drug Induced Liver Injury (DILI) ............................................ 
 
9.2.8 Other Safety Considerations .................................................................... 
 
9.3 Overdose ........................................................................................................... 
 
9.4 Safety ................................................................................................................ 
 
9.4.1 Physical Examinations ............................................................................. 
 
9.4.1.1 Medical Photography...................................................................... 
 
9.4.2 Vital signs................................................................................................. 
 
9.4.3 Electrocardiograms ................................................................................. 
 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
 
9.4.5 Imaging Safety Assessment ...................................................................... 
 
9.5 Pharmacokinetics .............................................................................................. 
 
9.6 Pharmacodynamics ........................................................................................... 
 
 
 
 
 
 
9.8 Biomarkers ........................................................................................................ 
 
9.8.1 Additional Research Collection ............................................................... 
 
9.8.2 Other Assessments ................................................................................... 
 
9.9 Health Economics OR Medical Resource Utilization and Health Economics . 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Sample Size Determination ............................................................................. 
 
10.2 Populations for Analyses ................................................................................ 
 
10.3 Statistical Analyses ......................................................................................... 
 
10.3.1 Efficacy Analyses ................................................................................... 
 
10.3.2 Safety Analyses....................................................................................... 
 
10.3.3 Other Analyses ....................................................................................... 
 
10.3.4 Interim Analyses ..................................................................................... 
 
11 REFERENCES ........................................................................................................ 
 
12 APPENDICES ......................................................................................................... 
 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
 
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APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW UP AND REPORTING ......................................................................... 
 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
 
APPENDIX 5 DIAGNOSTIC CRITERIA FOR DRUG AND ALCOHOL ABUSE .. 
 
APPENDIX 6 CYP3A4 AND CYP2B6 GUIDANCE ................................................. 
 
APPENDIX 7 INTERPRETATION OF HEPATITIS B SEROLOGICAL TEST 
RESULTS ............................................................................................................... 
 
 
 
APPENDIX 9 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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SYNOPSIS
Not applicable.
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SCHEDULE OF ACTIVITIES
Study assessment and procedures for screening are presented in Table 2-1, and on-treatment 
assessments and procedures are presented in Table 2-2 (Treatment Arms 1, 2, and 3) and Table 2-
3 for Treatment Arm 4.
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Table 2-1:
Screening Procedural Outline (CV006037)
Procedure
Screening Visit
(Day -28 to Day -1)
Day -7 to -1
Optional Run-in 
Period
Notes
Eligibility Assessments
Informed Consent
X
A participant is considered enrolled only when a protocol specific 
informed consent is signed.
Inclusion/Exclusion Criteria
X
Medical History
X
Include any toxicities or allergy related to previous treatments.
Include any COVID-19 history, including vaccinations.
Safety Assessments
Physical Examination 
X
Physical Measurements
X
Height and weight at screening. Body mass index will be 
calculated at screening.
Vital Signs
X
Includes body temperature, respiratory rate, and seated blood 
pressure and heart rate. Blood pressure and heart rate should be 
measured after the participant has been resting quietly for at least 
5 minutes.
Electrocardiogram
X
Electrocardiograms should be recorded after the participant has 
been supine for at least 5 minutes. 
Clinical Laboratory Tests
X
Includes blood and urine samples. See Section 9.4.4. Participants 
are required to fast for at least 10 hours prior to the collection of 
specimens for clinical laboratory tests. Results must be reviewed 
by the investigator prior to admission on Day 1.
Serology
X
Includes hepatitis C antibody, hepatitis B surface antigen, and 
HIV-1 and -2 antibodies. Results must be reviewed by the 
investigator prior to admission on Day 1.
Urine Drug Test
X
Includes alcohol. Screening results must be available and 
reviewed prior to admission on Day 1.
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Table 2-1:
Screening Procedural Outline (CV006037)
Procedure
Screening Visit
(Day -28 to Day -1)
Day -7 to -1
Optional Run-in 
Period
Notes
Serum Pregnancy Test
X
For WOCBP only. See Section 9.4.4. Screening results must be 
reviewed prior to admission on Day 1.
Follicle-Stimulating Hormone
X
Postmenopausal women only. See Section 9.4.4 and Appendix 4.
Prior Medication Use
X
History of prior medications will be assessed.
Optional Run-in Period
Ticagrelor BID, Aspirin, or Ticagrelor 
BID/Aspirin Administration
X
Participants who are not previously taking ticagrelor BID, 
aspirin, or ticagrelor BID + aspirin will be required to take 1 of 
the medications for at least 7 days prior to Day 1 to ensure steady 
state has been attained. This is not required for healthy 
participants enrolled in Treatment Arm 4.
Adverse Event Reporting
Monitor for Non-Serious Adverse 
Events
X
Collected only for participants who participate in the Run-in 
Period.
Monitor for SAEs
X
X
All SAEs must be collected from the date of participant’s written 
consent until 30 days after the last dose of study treatment or 
participant’s participation in the study.
Abbreviations: BID = twice daily; HIV = human immunodeficiency virus; SAE = serious adverse event; WOCBP = women of childbearing potential
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Table 2-2:
On Treatment Procedural Outline (CV006037) - Treatment Arms 1, 2, and 3
Procedure
Day 1
(Visit 1)
Day 2
(Visit 2/Clinic
Dischargea)
Day 8/
Study 
Discharge
Notes
Check-in Assessments
Inclusion/Exclusion Criteria
X
Medical History
X
Interim medical history collected before dosing on Day 1. 
Include any toxicities or allergy related to previous 
treatments.
Prior Medication Use
X
History of prior medications will be assessed before dosing 
on Day 1.
Report to Study Site
X
X
In the morning on Day 1, participants will report to the study 
site prior to the baseline chamber run. Participants will be 
released from the clinic after the Hour 2 chamber run is 
complete and the PK sample is collected. Participants will 
return to the study site approximately 1 hour before the final 
chamber run on Day 2.
Safety Assessments
Physical Examination 
X
X
If the screening physical examination is performed within 
24 hours prior to dosing on Day 1, then a single exam may 
count as both the screening and predose evaluation.
Physical examinations will be performed at check-in (if the 
screening physical examination is performed more than 
24 hours prior to dosing on Day 1) and after the chamber run 
on Day 2.
Standard baseline photographs of any area with clinical 
findings will be taken. See Section 9.4.1.1
Physical Measurements
X
X
Weight only at check-in and Day 2. Body mass index will be 
calculated before dosing on Day 1.
Vital Signs
X
X
See note in screening procedures.
Vital signs will be obtained at check-in and prior to and after 
each chamber assessment on Days 1 and 2.
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Table 2-2:
On Treatment Procedural Outline (CV006037) - Treatment Arms 1, 2, and 3
Procedure
Day 1
(Visit 1)
Day 2
(Visit 2/Clinic
Dischargea)
Day 8/
Study 
Discharge
Notes
Electrocardiogram
X
X
See note in screening procedures.
Electrocardiograms will be collected at check-in, and 2 and 
24 hours after BMS-986141 dosing. The 2-hour and 24-hour 
ECGs should be performed prior to the Badimon Chamber 
run.
Clinical Laboratory Tests
X
X
See note in screening procedures and Section 9.4.4. 
Laboratory tests will be collected at check-in, and 2 and 
24 hours after BMS-986141 dosing.
Urine Drug Test
X
See note in screening procedures.
Performed at check-in; results must be reviewed before 
BMS-986141 dosing on Day 1.
Pregnancy Test
X
Performed at check-in; results must be reviewed prior to 
BMS-986141 dosing on Day 1.
Concomitant Medication Use
X
X
X
Monitor for Non-Serious Adverse Events
X
X
X
Monitor for Serious Adverse Events
X
X
X
See note in screening procedures.
Follow-up Telephone Call
X
±2 days. The scheduled follow-up telephone call will include 
review of the specific follow-up instructions and clinically 
pertinent re-assessment regarding those recommendations 
which are being provided to the participant to resume any 
prior medications, including, but not limited to, specific anti-
platelet therapeutics.
PK Assessments
Serial Blood PK Sampling
X
X
See Table 9.5-1, Table 9.5-2, and Table 9.5-3.
Thrombosis Chamber Procedure
X
X
See Section 9.8.
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Table 2-2:
On Treatment Procedural Outline (CV006037) - Treatment Arms 1, 2, and 3
Procedure
Day 1
(Visit 1)
Day 2
(Visit 2/Clinic
Dischargea)
Day 8/
Study 
Discharge
Notes
Each participant will undergo a total of 3 thrombosis 
chamber procedures.
Biomarker Assessments
See Section 9.8.
 
 
X
X
 
X
Serum collection for SARS-CoV-2 
serology
X
See Table 9.8-1.
Serum collected to be used for measurements of 
anti-SARS-CoV-2 serology.
Clinical Drug Supplies
Ticagrelor BID or Aspirin, or Ticagrelor 
BID + Aspirin Administration
X
X
Those sourced by the investigator.
BMS-986141 Administration
X
Those supplied by BMS.
a Evaluations performed prior to study discharge, or for participants who are prematurely discontinued.
Abbreviations: ADME = absorption, distribution, metabolism, and elimination; BID = twice daily; DNA = deoxyribonucleic acid; PD = pharmacodynamic; 
PK = pharmacokinetic
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Table 2-3:
On Treatment Procedural Outline (CV006037) - Treatment Arm 4
Procedure
Day 1
(Visit 1)
Day 2
(Visit 2/Clinic 
Dischargea)
Day 8/
Study Discharge
Notes
Check-in Assessments
Inclusion/Exclusion Criteria
X
Medical History
X
Interim medical history collected before dosing 
on Day 1. Include any toxicities or allergy 
related to previous treatments.
Prior Medication Use
X
History of prior medications will be assessed 
before dosing on Day 1.
Report to Study Site
X
X
In the morning on Day 1, participants will report 
to the study site prior to the baseline chamber 
run. Participants will be released from the clinic 
after the Hour 2 chamber run is complete and the 
PK sample is collected. Participants will return 
to the study site approximately 1 hour before the 
final chamber run on Day 2.
Safety Assessments
Physical Examination 
X
X
If the screening physical examination is 
performed within 24 hours prior to dosing on 
Day 1, then a single exam may count as both the 
screening and predose evaluation.
Physical examinations will be performed at 
check-in (if the screening physical examination 
is performed more than 24 hours prior to dosing 
on Day 1) and after the chamber run on Day 2.
Standard baseline photographs of any area with 
clinical findings will be taken. See Section 
9.4.1.1.
Physical Measurements
X
X
Weight only at check-in and Day 2. Body mass 
index will be calculated before dosing on Day 1.
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Table 2-3:
On Treatment Procedural Outline (CV006037) - Treatment Arm 4
Procedure
Day 1
(Visit 1)
Day 2
(Visit 2/Clinic 
Dischargea)
Day 8/
Study Discharge
Notes
Vital Signs
X
X
See note in screening procedures.
Vital signs will be collected at check-in and 
prior to and after each chamber assessment on 
Days 1 and 2.
Electrocardiogram
X
X
See note in screening procedures.
Electrocardiograms will be collected at check-in, 
and 2 and 24 hours after dosing. The 2-hour and 
24-hour ECGs should be performed prior to the 
Badimon Chamber run.
Clinical Laboratory Tests
X
X
See note in screening procedures and 
Section 9.4.4.
Laboratory tests will be collected at check-in, 
and 2 and 24 hours after dosing.
Urine Drug Test
X
See note in screening procedures.
Performed at check-in; results must be reviewed 
before dosing on Day 1.
Pregnancy Test
X
Performed at check-in; results must be reviewed 
prior to dosing on Day 1.
Concomitant Medication Use
X
X
X
Monitor for Non-Serious Adverse Events
X
X
X
Monitor for Serious Adverse Events
X
X
X
See note in screening procedures.
Follow-up Telephone Call
X
±2 days. The scheduled follow-up telephone call 
will include review of the specific follow-up 
instructions and clinically pertinent re-
assessment regarding those recommendations 
which are being provided to the participant to 
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Table 2-3:
On Treatment Procedural Outline (CV006037) - Treatment Arm 4
Procedure
Day 1
(Visit 1)
Day 2
(Visit 2/Clinic 
Dischargea)
Day 8/
Study Discharge
Notes
resume any prior medications, including, but not 
limited to, specific anti-platelet therapeutics.
PK Assessments
Serial Blood PK Sampling
X
X
See Table 9.5-4.
Thrombosis Chamber Procedure
X
X
See Section 9.8.
Each participant will undergo a total of 
3 thrombosis chamber procedures.
Biomarker Assessments
See Section 9.8.
 
 
 
Serum collection for SARS-CoV-2 serology
X
See Table 9.8-2.
Serum collected to be used for measurements of 
anti-SARS-CoV-2 serology.
Clinical Drug Supplies
BMS-986141 Administration
X
Those supplied by BMS.
a Evaluations performed prior to study discharge, or for participants who are prematurely discontinued.
Abbreviations: ADME = absorption, distribution, metabolism, and elimination; DNA = deoxyribonucleic acid; PD = pharmacodynamic; PK = pharmacokinetic
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In the event that multiple procedures are required at a single time point, the electrocardiogram 
(ECG) and vital signs may be obtained up to 15 minutes earlier, and clinical laboratory samples
may be obtained up to 5 minutes earlier than the nominal time point, ensuring the pharmacokinetic 
(PK) samples, biomarker samples, and Badimon Chamber samples can be collected on time.
3
INTRODUCTION
Atherothrombotic diseases such as ischemic stroke, transient ischemic attack (TIA), and acute 
coronary syndrome represent areas of unmet medical need which would likely benefit from 
improved therapies. Ischemic stroke represents a particularly high unmet need as attempts to 
reduce stroke recurrence have often failed to improve the net clinical benefit because 
improvements in efficacy have only been possible with a concomitant increase in the risk of serious 
bleeding, including intracranial hemorrhage. Acetylsalicylic acid (ASA) has remained the standard 
of care for secondary prevention after ischemic stroke and TIA because of its perceived low risk 
of bleeding. In studies to date, treatment with more intensive antiplatelet therapy have 
demonstrated a reduction in the risk for TIA and stroke.1
Each year stroke occurs in approximately 15 million people worldwide. It is responsible for almost 
6 million deaths and an additional 5 million individuals are permanently disabled.2 In the United 
States, nearly 800,000 people experience TIA or stroke every year, with approximately 87% of 
these events being due to cerebral ischemia.3
TIA and ischemic stroke share a common atherothrombotic pathophysiology, but prognosis varies 
depending on severity and cause. Current criteria define a TIA as a transient episode of 
neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute 
infarction. The 90-day risk of stroke following TIA is as high as 17% with the greatest risk apparent 
in the first week. Patients at highest risk may be identified through neurological assessment scores 
(ABCD2), ultrasound, and magnetic resonance imaging. 
Acetylsalicylic acid has been shown to have modest efficacy, with a 13% reduction in recurrent 
stroke (odds ratio 0.87, 95% confidence interval [CI] 0.79, 0.97).4 Alternative antiplatelet therapies 
or combinations of therapies to improve upon the efficacy of ASA have been sought for many 
years. The results of the CHANCE study, which examined the use of dual antiplatelet therapy in 
Chinese patients after acute TIA and minor stroke, suggested that dual antiplatelet therapy may 
show clinical benefit without increased bleeding risk, but the applicability of these results to 
patients in other countries awaits confirmation.5 It remains clear that improved antiplatelet agents 
with an improved benefit risk profile are needed to help alleviate this significant unmet medical 
need.
3.1
Study Rationale
The effectiveness of antithrombotic agents on thrombus formation cannot be assessed in healthy 
participants (ie, participants without an active thrombotic process and thrombus formation) with 
conventional clinical tools. While such agents may alter biomarker measures of coagulation (eg, 
international normalized ratio [INR] and activated partial thromboplastin time [aPTT]) or platelet 
activity (eg, platelet aggregation) in both animals and in healthy participants, early phase studies 
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are limited in their potential to determine the clinical efficacy of novel antithrombotic 
compounds.6,7 Advances in ex vivo thrombosis assays, however, may overcome these limitations 
and lead to new methods for evaluating antithrombotic agents including strategies for optimized 
dose and schedule selection.
Several ex-vivo perfusion chamber systems have been developed to investigate the mechanisms 
of thrombus formation. These systems are not dependent on the presence of active thrombotic 
disease as thrombus formation is stimulated by exposure of flowing blood to an exogenous 
thrombogenic substrate under controlled conditions. The most widely employed flow devices are 
the annular perfusion chamber and the parallel-plate perfusion chamber.6,7 These systems have 
been successfully used to evaluate the effects of marketed antithrombotic drugs on thrombus 
formation in vitro and ex vivo in human participants, including differential effectiveness in high 
(arterial) and low (venous) shear environments dependent thrombus formation.7,8,9,10,11,12
This study will be performed using a Badimon perfusion chamber under well controlled rheologic 
conditions that simulate patent arteries (low shear rate, approximately 212 s-1) and stenosed 
arteries (high shear rate, approximately 1690 s-1). This perfusion chamber allows for the evaluation 
of thrombus formed on carefully prepared strips of porcine aorta (from which the intima and a thin 
layer of media had been removed) thrombogenic surface exposed to blood flowing directly from 
the participant’s antecubital vein through the perfusion chamber. This experimental thrombosis 
model allows assessment of thrombus formation by morphometry. Antithrombotic effects can be 
quantified by the amount (in this case, reduction) of thrombus formed on the exposed substrate.
The primary objective of this study is to assess the effect of BMS-986141 on thrombus formation
in an ex-vivo porcine aortic thrombosis chamber model. Key secondary objectives are to assess 
the safety and tolerability of BMS-986141 when given with aspirin, ticagrelor, or with aspirin and 
ticagrelor in participants with coronary artery disease; to assess the safety of aspirin alone, 
ticagrelor alone, and the combination of aspirin and ticagrelor in participants with coronary artery 
disease; and to assess the safety and tolerability of a single dose of BMS-986141 in normal healthy 
participants.
3.2
Background
BMS-986141 is a novel, highly selective, potent, and orally active antagonist of protease-activated 
receptor 4 (PAR4). PAR4 is a G-protein coupled receptor present on human platelets.13 It is 
activated by thrombin, a key enzyme in the coagulation cascade. Evidence suggests that PAR4 
plays a role in the later stages of platelet activation,14,15,16,17 which is thought to be more important 
for propagation of thrombus growth and arterial occlusion and less important for hemostasis.18,19
Consistent with this hypothesis, a cynomolgus monkey model was utilized to demonstrate that 
BMS-986141 significantly inhibited occlusive thrombus formation with almost no impact on 
hemostasis. This large window between antithrombic efficacy and bleeding safety suggests that 
BMS-986141 has potential as a novel therapeutic agent for the treatment of atherothrombotic 
diseases such as acute TIA and minor stroke.
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A detailed description of the pharmacology, toxicology, metabolism, and safety of BMS-986141 
is provided in the Investigator’s Brochure (IB).20
3.2.1
Nonclinical Pharmacology and Pharmacokinetics
With an equilibrium binding constant of 0.102 nM for human PAR4, BMS-986141 inhibited PAR4 
agonist peptide (AP)-induced cellular calcium mobilization with a concentration at which 50% 
inhibition observed (IC50) value of 0.45 nM. BMS-986141 is selective for PAR4 because it was 
ineffective at blocking calcium mobilization stimulated by selective activation of either human 
protease-activated receptor-1 (PAR1) or human protease-activated receptor-2 (PAR2). In addition, 
BMS-986141 showed no inhibitory activity when tested against a panel of purified proteases that 
included thrombin as well as other major coagulation enzymes.
BMS-986141 demonstrated potent, selective, and reversible inhibition of platelet aggregation in 
vitro and ex vivo.21 When gamma-thrombin, a selective PAR4 activator, was utilized to stimulate 
aggregation in human platelet-rich plasma, aggregation was completely inhibited by BMS-986141 
with an IC50 value of 2.1 nM. When alpha-thrombin, a dual PAR1 and PAR4 activator, was 
utilized to stimulate aggregation in washed platelets, BMS-986141 showed significant but partial 
inhibition of aggregation (up to 76%), suggesting that inhibition of PAR4 can diminish platelet 
aggregation even in the presence of PAR1 activation. In a whole blood aggregation assay, 
BMS-986141 inhibited aggregation stimulated by a selective PAR4-AP. BMS-986141 was 
ineffective at preventing platelet aggregation when blood was stimulated with non-PAR4 platelet 
activators including adenosine diphosphate (ADP), collagen, PAR1-AP, and a thromboxane A2 
mimetic.
Absolute oral bioavailability (F) of BMS-986141 given as a spray-dried dispersion suspension 
formulation was 25% to 36% in rats, dogs, and monkeys. When BMS-986141 was dosed as a 
solution or crystalline suspension in rats, F was 74% and 3.6%, respectively, indicating that the F 
of BMS-986141 is formulation-dependent.22
BMS-986141 and its major metabolite, 
BMT-162856, were not substrates for efflux transport in the Caco-2 cell model.23,24 The apparent 
elimination half-life (T-HALF) of BMS-986141 was 3.7, 12.8, and 74.7 hours in rats, dogs, and 
monkeys, respectively, and total plasma clearance was 8.5 mL/min/kg to 14.3 mL/min/kg. The 
corresponding blood clearance rates were equivalent to ≤ 28% of the respective reported liver 
blood flows.
The volume of distribution at steady state (Vss) in rats, dogs, and monkeys was greater than the 
respective species’ reported plasma volumes, indicative of extravascular distribution. 
BMS-986141 and its metabolite BMT-162856 were ≥ 99.4% bound to serum proteins in humans 
and nonclinical species; BMS-986141 was not distributed preferentially into either plasma or 
blood cells.22,23,24
In vitro PK drug-drug interaction evaluations showed minimal potential for BMS-986141 to act as 
a perpetrator for cytochrome P450 (CYP) 3A4 inhibition or induction at clinically relevant dose 
range (eg, up to 20 mg of BMS-986141). Additional details can be found in the IB.20
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3.2.2
Nonclinical Toxicity
There were no adverse findings in 28-day preclinical toxicology studies. In 3-month studies, the 
major preclinical findings of note were microscopic changes in the kidneys of some of the monkeys 
that received the highest dose of BMS-986141, 75 mg/kg/day. These changes have been 
characterized as moderate degeneration and regeneration of tubular epithelium, and the effect was 
not observed 1 month after cessation of dosing. There is no evidence of fetal toxicity/teratogenicity 
in expanded range-finding studies in pregnant rats and rabbits. No cardiovascular safety issues 
were identified.
Single oral doses of BMS-986141 up to 75 mg/kg were well tolerated in monkeys (maximum 
observed concentration [Cmax] ≤ 2.66 µg/mL; area under the concentration-time curve from time 
zero to 24 hours after dose [AUC(0-24)] ≤ 31.9 µg•h/mL), with no BMS-986141 related effects at 
any dose.
Repeat-dose toxicity studies were conducted at once daily oral doses ranging from 5 mg/kg/day to 
150 mg/kg/day in rats and mice, and from 5 mg/kg/day to 75 mg/kg/day in monkeys.
Area under the concentration-time curve [AUC] exposures were dose proportional up to 
25 mg/kg/day and less than dose proportional at higher doses in all species, with no sex differences 
observed in mean AUC values. The major metabolite, BMT-162856, was profiled in the 3-month 
toxicity studies in rats and monkeys as well as the 2-week mouse toxicokinetic/tolerability study. 
Exposure to the metabolite was 0.5× to 2.5× that of BMS-986141. Exposures (AUC and Cmax) at 
the end of the study in the 1-month rat and 3-month monkey toxicity studies were approximately 
70% less than those measured after the first dose. The cause for this decreased exposure is 
unknown, but it is not likely due to increased metabolism based on the lack of effect on liver 
weights or pathology, similar decrease in systemic exposures (AUC and Cmax) to the metabolite 
BMT-162856, and no evidence of increased hepatic gene expression of a panel of enzymes 
(CYP2B1, CYP3A23/3, CYP4A2, enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase, or 
pyruvate dehydrogenase kinase 4) in rats.25
3.2.3
Clinical Pharmacology and Safety
Pharmacokinetic data shows that BMS-986141 was rapidly absorbed following single or multiple 
doses, with time of maximum observed concentration (Tmax) ranging from 1 hours to 4 hours and 
the terminal T-HALF of approximately 22 hours. Following multiple administration of 
BMS-986141 (daily doses of 0.3, 2, 10, and 30 mg) for 14 days, there was a slight accumulation 
of area under the concentration-time curve over the dosing interval (AUC[TAU]) for 
BMS-986141. The accumulation indexes for AUC(TAU) were less than 2 (ranged from 1.3 to 
1.9 across different doses). Both Cmax and AUC of BMS-986141 increased in an approximately 
dose-proportional manner up to a single dose of 150 mg and multiple doses of 30 mg.
Pharmacodynamics (PD) of BMS-986141 are assessed by ex vivo PAR4-AP-induced platelet 
aggregation. PD data demonstrated dose-
and concentration-dependent inhibition of 
PAR4-AP-induced platelet aggregation in an almost dichotomous appearance, with the 
on-set/off-set of inhibition occurring approximately at mean BMS-986141 concentration of 0.5 
and 1.5 ng/mL for PAR4-AP concentrations of 12.5 and 25 µM, respectively. This result is 
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consistent with preclinical findings indicating competitive interaction between BMS-986141 and 
PAR4-AP.
BMS-986141 has a safe and well tolerated profile in over 100 healthy volunteers across 5 Phase 1 
studies using a wide dose range in both single and multiple doses (across 14 days).
3.3
Benefit/Risk Assessment
Participants will receive no known health benefit from participating in the study beyond that of an 
assessment of their overall health status.
BMS-986141 is a highly selective antagonist of PAR4, a thrombin-activated receptor found on 
human platelets. In animals, BMS-986141 has shown to block thrombosis with minimal increased 
in bleeding, even when combined with aspirin.26
BMS-986141 has a safe and well tolerated profile in over 100 healthy volunteers across 5 Phase 1 
studies using a wide dose range in single and multiple doses. The clinical pharmacology profile 
complements the mechanism of action and optimizes the benefit/risk ratio compared to other 
antiplatelet agents that have some disadvantages (eg, irreversible, pro-drug).
The impact of BMS-986141 influencing the exposures of ticagrelor or aspirin (and its major 
metabolite salicylic acid), is based on the nonclinical evaluation of drug interaction potential as a 
perpetrator. Exposures of BMS-986141 are expected to stay within the range of exposures that 
have been found to be safe in the single and multiple dose studies. The doses of ticagrelor and 
aspirin used in this study have been used in other drug-drug interaction studies and have an 
acceptable safety profile.
BMS-986141 is not expected to have an impact on the PD (platelet aggregation) of ticagrelor, 
aspirin, or its major metabolite, salicylic acid based on the mechanism of action, preclinical data 
of PAR4 antagonists, and data from the Phase 1 studies.
There is a small risk of increased bleeding in the dual therapy and triple therapy treatment arms; 
however, based on accumulated data of previous studies, no major bleeding events using 
BMS-986141 alone have been observed. Participants who do not currently receive any antiplatelet 
therapy, or who are currently on aspirin alone as their standard of care, will be excluded from 
Treatment Arm 3 (triple therapy).
Risks from the phlebotomy and perfusion chamber procedures are standard and include infection, 
bleeding, bruising, blood clot formation, discomfort at the phlebotomy site, and fainting.
Selected participants, who are currently taking clopidogrel, will be switched to ticagrelor for study 
purposes. Ticagrelor has been shown to be a more potent antiplatelet agent and to provide better 
antithrombotic protection in selected patient populations with minimal effects on bleeding 
liabilities compared to clopidogrel. Guidance for return to previous therapies is provided in Section 
7.9.
Ticagrelor and aspirin are both marketed drugs and have substantial clinical use, both individually 
and in combination. These marketed drugs may prolong bleeding time and increase the risk of 
bleeding events such as gastrointestinal bleeding. An increased bleeding risk with dual antiplatelet 
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therapy in patients has been observed but is most relevant to high-risk patients with vascular 
disease and to longer periods of treatment.
The most commonly reported adverse effects associated with the administration of ticagrelor 
include dizziness, nausea, shortness of breath, chest pain, irregular heartbeat, rash, and swelling of 
the face, throat, tongue, lips, and eyes.
The most commonly reported adverse effects associated with the administration of aspirin include 
dizziness, nausea, vomiting, diarrhea, dyspepsia, heartburn, elevated bilirubin, elevated liver 
function laboratory tests (liver transaminase, blood urea nitrogen, and creatinine), skin rash, and 
tinnitus.
If the efficacy and safety profile of PAR4 antagonists in nonclinical studies can be confirmed in 
humans, BMS-986141 could represent an important advancement in the treatment and prevention 
of arterial thrombotic disorders.
4
OBJECTIVES AND ENDPOINTS
Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Primary

To assess the effect of BMS-986141 alone and as add on to ticagrelor, 
aspirin, or the ticagrelor + aspirin combination, on thrombus formation 
in an ex vivo porcine aortic thrombosis chamber model as compared to 
pretreatment

Change
from baseline in 
thrombus area (post-treatment 
with 
BMS-986141
versus
pretreatment)
Secondary

To assess the safety and tolerability of single doses of BMS-986141 
when dosed with ticagrelor, aspirin, or the ticagrelor + aspirin 
combination

AEs, 
clinical 
laboratory 
values, vital signs, ECGs, or 
other safety biomarkers

To assess the safety and tolerability of ticagrelor, aspirin, or the ticagrelor 
+ aspirin combination in participants with coronary artery disease

AEs, 
clinical 
laboratory 
values, vital signs, ECGs, or 
other safety biomarkers

To assess the safety and tolerability of a single dose of BMS-986141 in 
normal healthy participants

AEs, 
clinical 
laboratory 
values, vital signs, ECGs, or 
other safety biomarkers
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5
STUDY DESIGN
5.1
Overall Design
This is an open-label, single-center, 4-arm study to assess the effect of BMS-986141 on thrombus 
formation in an ex vivo porcine aortic thrombosis chamber model as compared to pretreatment 
with BMS-986141. Participants will be screened to determine eligibility within 28 days prior to 
study treatment.
An optional Run-in Period will take place after screening if participants are taking a similar 
antiplatelet drug (eg, clopidogrel), a lower dose of ticagrelor twice daily (BID), aspirin, or 
ticagrelor BID + aspirin or are not currently taking ticagrelor BID, aspirin, or ticagrelor BID + 
aspirin as part of their standard of care. Participants will receive ticagrelor BID, aspirin, or 
ticagrelor BID + aspirin daily for at least 7 days under the supervision of the investigator prior to 
Day 1. The timing of each dose and number of tablets taken will be recorded in a diary. Diaries
will be reviewed by study site personnel on Day 1. Participants who do not have 100% compliance 
will not continue in the study. Participants who do not currently receive any antiplatelet therapy, 
or who are currently on aspirin alone as their standard of care, will be excluded from Treatment 
Arm 3 (triple therapy).
Approximately 15 participants each with a confirmed history of (must have at least 1 of the 
following conditions) proven coronary artery disease (greater than 50% stenosis of proximal 
coronary artery), prior coronary revascularisation (percutaneous coronary intervention or coronary 
artery bypass grafting), and/or prior myocardial infarction will be enrolled to 1 of 3 treatment arms 
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(15 participants per arm, based on their background therapy). Treatment arms will not be 
randomized but instead be allocated as open-label at the discretion of the Principal Investigator as 
shown below. Enrollment will require that Treatment Arms 1-3 shall enroll 15 participants each 
while Treatment Arm 4 (healthy volunteers) will enroll 10 participants.

Treatment Arm 1:  Single oral dose of 90 mg ticagrelor alone, followed by a single oral dose 
of 4 mg BMS-986141 approximately 2 hours later (Day 1). A second dose of ticagrelor will be 
taken approximately 12 hours after the first dose. Twice daily dosing of ticagrelor will be 
continued on Day 2.

Treatment Arm 2:  Single oral dose of 75 mg aspirin alone, followed by a single oral dose of 
4 mg BMS-986141 approximately 2 hours later (Day 1). Daily dosing of aspirin will continue 
on Day 2.

Treatment Arm 3:  Single oral dose of 90 mg ticagrelor + 75 mg aspirin, followed by a single 
oral dose of 4 mg BMS-986141 approximately 2 hours later (Day 1). A second dose of 
ticagrelor will be taken approximately 12 hours after the first dose. Ticagrelor + aspirin dosing 
will continue on Day 2.
Approximately 10 normal healthy participants will be enrolled in Treatment Arm 4 and receive a 
single dose of 4 mg BMS-986141 on Day 1.
Participants will report to the clinical facility in the morning on Day 1 (Visit 1) prior to 
BMS-986141 dosing and will return to the clinical facility on Day 2 (Visit 2) approximately 1 hour 
prior to the final chamber run. Thrombus formation will be determined using the Badimon 
thrombosis chamber, according to the standard site procedures. Briefly, each participant will have 
blood drawn from a vein through a cannula set attached to extension tubing. The tubing will be 
connected to a series of 3 perfusion chambers containing denuded porcine aorta as a thrombogenic 
surface. A pump placed distal to the chambers will maintain a unidirectional flow at a rate of 
10 mL/min. The rheologic conditions in the first chamber will be at a low shear rate (approximately 
212 s-1) simulating patent arterial flow. The shear rate on the second and third chambers will be 
high (approximately 1690 s-1), simulating stenosed arteries. Each perfusion study will last for 
5 minutes. The size of the thrombus formed on the denuded porcine aorta will be assessed by 
morphometrical analysis. A total of 3 perfusion runs will be performed per participant in each 
treatment arm.
For Treatment Arms 1, 2, and 3, a baseline chamber run will be performed on Day 1 approximately 
2 hours after background therapy (ticagrelor, aspirin, or ticagrelor + aspirin) and prior to 
BMS-986141 administration. A second chamber run will be performed 2 hours following oral 
administration of BMS-986141. This second chamber run is designed to be conducted at the 
predicted Tmax of BMS-986141. Participants will be released from the clinic after the Hour 2 
chamber run is complete and the Hour 2 PK sample is collected. Participants will return to the 
clinic on Day 2 approximately 1 hour before the final chamber run. Participants will receive 
background therapy before the final chamber run, and the final chamber run will be performed on 
Day 2, approximately 24 hours after BMS-986141 dosing. Participants will be discharged from 
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the clinic after the conclusion of this chamber run, with final discharge from the study following 
telephone follow-up on Day 8 (±2 days).
For Treatment Arm 4, a baseline chamber run will be performed on Day 1 prior to BMS-986141 
administration. A second chamber run will be performed 2 hours following oral administration of 
BMS-986141. This second chamber run is designed to be conducted at the predicted Tmax of 
BMS-986141. Participants will be released from the clinic after the Hour 2 chamber run is 
complete and the Hour 2 PK sample is collected. Participants will return to the clinic on Day 2 
approximately 1 hour before the final chamber run. The final chamber run will be performed 
approximately 24 hours after dosing. Participants may be discharged from the clinic after the 
conclusion of this chamber run, with final discharge from the study following telephone follow-up 
on Day 8 (±2 days).
The study design schematic is presented in Figure 5.1-1.
Figure 5.1-1:
Study Design Schematic
Treatment Arm 1
Day 1
(Visit 1)
Day 2
(Visit 2)
Day 8
(±2 days)
2 hours 
postdose
24 hours 
postdose
Follow-up 
telephone 
call
Baseline 
Chamber
Tmax 
Chamber
Final 
Chamber
S, E, T
~2 hours after 
Ticagrelor
BMS-986141 
4 mg
Leave after 
Hour 2
chamber 
run/PK sample
Ticagrelor
(~2 hours 
prior to Final 
Chamber)
CD
D
Treatment Arm 2
Day 1
(Visit 1)
Day 2
(Visit 2)
Day 8
(±2 days)
2 hours 
postdose
24 hours 
postdose
Follow-up 
telephone 
call
Baseline 
Chamber
Tmax 
Chamber
Final 
Chamber
S, E, A
~2 hours after 
Aspirin
BMS-986141 
4 mg
Leave after 
Hour 2 
chamber 
run/PK 
sample
Aspirin
(~2 hours 
prior to Final 
Chamber)
CD
D
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Abbreviations: A = aspirin; CD = clinic discharge; D = study discharge; E = enrollment; PK = pharmacokinetic; 
S = screening; T = ticagrelor; T/A = ticagrelor + aspirin; Tmax = time of maximum observed concentration
Physical examinations, vital sign measurements, 12-lead ECGs, and clinical laboratory evaluations 
will be performed at selected times throughout the dosing interval. Participants will be closely 
monitored for adverse events (AEs) throughout the study. Blood samples will be collected for up 
to 24 hours after study drug administration for PK and biomarker analysis. Less than 380 mL of 
blood will be drawn from each participant during the study.
5.1.1
Data Monitoring Committee and Other External Committees
Not applicable.
5.2
Number of Participants
Approximately 55 participants (15 participants each in Treatment Arms 1, 2, and 3 and 
10 participants in Treatment Arm 4) are planned to be dosed. Sample size determination is 
discussed in Section 10.1.
5.3
End of Study Definition
The start of the trial is defined as first visit for the first participant screened. End of trial is defined 
as the date of the last health status follow-up contact made to the last participant discharged from 
Treatment Arm 3
Day 1
(Visit 1)
Day 2
(Visit 2)
Day 8
(±2 days)
2 hours 
postdose
24 hours 
postdose
Follow-up 
telephone 
call
Baseline 
Chamber
Tmax 
Chamber
Final 
Chamber
S, E, T/A
~2 hours 
after T/A
BMS-986141 
4 mg
Leave after 
Hour 2 
chamber 
run/PK 
sample
T/A
(~2 hours 
prior to Final 
Chamber)
CD
D
Treatment Arm 4
Day 1
(Visit 1)
Day 2
(Visit 2)
Day 8
(±2 days)
Baseline
2 hours 
postdose
24 hours 
postdose
Follow-up 
telephone 
call
Baseline 
Chamber
Tmax 
Chamber
Final 
Chamber
S, E 
BMS-986141 
4 mg
Leave after 
Hour 2 
chamber 
run/PK 
sample
CD
D
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the study. Study completion is defined as the final date on which data for the primary endpoint 
was or is expected to be collected, if this is not the same.
The approximate duration of this study will be 36 days, including a 28-day screening period and 
an 8-day treatment period.
5.4
Scientific Rationale for Study Design
To characterize the ability of BMS-986141 at a dose of 4 mg to reduce thrombus formation in an 
ex vivo porcine aortic thrombosis chamber model as compared to ticagrelor BID, aspirin, or 
ticagrelor BID + aspirin for participants with coronary artery disease. To characterize the ability 
of BMS-986141 at a dose of 4 mg to reduce thrombus formation in an ex vivo porcine aortic 
thrombosis chamber model in healthy participants.
5.5
Justification for Dose
Single doses of BMS-986141 have been evaluated up to 150 mg and multiple doses up to 30 mg 
once daily for up to 14 days in study CV006003 with acceptable safety and tolerability. 
BMS-986141 has also been dosed 20 mg once daily for 14 days in the presence of 325 mg aspirin. 
No appreciable changes in PK, PD, or bleeding time were observed in the presence of aspirin. The 
PK were found to be dose proportional in the explored range. BMS-986141 is characterized by 
rapid absorption with maximal concentrations at 1 to 4 hours postdose and a terminal half-life of 
about 40 hours. Evaluation of exposures after daily dosing indicates an accumulation index of up 
to 1.9 and an effective half-life of about 22 hours, suggestive that once daily dosing would be 
suitable. Integration of mechanistic, cyno-electrically-mediated carotid arterial thrombosis
(ECAT) concentration-response data with PK/PD platelet aggregation utilizing 12.5, 25, 50 and 
100 uM AP suggest that concentrations of BMS-986141 need to exceed certain thresholds to 
maintain efficacious inhibition of platelets. Thus, dose selection utilizes steady state trough 
concentrations as an efficacy target. Upon dosing 4 mg of BMS-986141, two Badimon chamber 
runs are planned. One at Tmax, which maximize the percentage of participants exceeding the 
ECAT drug concentration that gives 80% of Emax (EC80), and the second 24 hours after dosing 
which will maximize the percentage of participants exceeding the ECAT concentration for 50% 
efficacy (EC50). This evaluation will allow for an assessment of thrombus size reduction at each 
ECAT target to support dose selection optimization under various background therapies including 
aspirin monotherapy, ticagrelor monotherapy, and dual antiplatelet therapy (aspirin + ticagrelor).
6
STUDY POPULATION
For entry into the study, the following criteria MUST be met.
6.1
Inclusion Criteria
1) Signed Written Informed Consent
a) Signed written informed consent must be obtained from the participants in accordance with 
the requirements of the study center’s Independent Ethics Committee (IEC) before 
initiation of any protocol-required procedures.
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2) Type of Participant and Target Disease Characteristics
a) Body mass index (BMI) 18.0 to 35.0 kg/m2, inclusive, with a body weight between 50 kg 
and 120 kg, inclusive. BMI = weight (kg)/(height [m])2 for participants.
b) For Treatment Arms 1, 2, and 3, participant has a history of or has been diagnosed with at 
least 1 of the following:
i)
Prior angiographically proven coronary artery disease (greater than 50% stenosis of 
proximal coronary artery)
ii) Prior coronary revascularisation (percutaneous coronary intervention or coronary 
artery bypass grafting)
iii) Prior myocardial infarction
c) For Treatment Arms 1, 2, and 3, participant is eligible as determined by no deviation from 
normal considered significant by the investigator in medical history, physical examination, 
12-lead ECG measurements, and clinical laboratory determinations, except for the 
cardiovascular history. 
d) For Treatment Arm 4, participant is healthy as determined by no deviation from normal 
considered significant by the investigator in medical history, physical examination, 12-lead 
ECG measurements, and clinical laboratory determinations.
3) Age and Reproductive Status
Investigators shall counsel women of childbearing potential (WOCBP) participants, and male 
participants who are sexually active with WOCBP, on the importance of pregnancy prevention 
and the implications of an unexpected pregnancy.

The investigator shall evaluate the effectiveness of the contraceptive method in relationship to 
the first dose of study intervention.

Local laws and regulations may require the use of alternative and/or additional contraception 
methods.
a) Female Participants 
i)
Females, ages 18 to 75 years, inclusive.
ii) Women who are not of childbearing potential are exempt from contraceptive 
requirements.
iii) Women participants must have documented proof that they are not of childbearing 
potential.
iv) WOCBP must have a negative highly sensitive serum pregnancy test (minimum 
sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 
24 hours prior to the start of study treatment.
v) Additional requirements for pregnancy testing during and after study intervention are 
located in Section 2, Schedule of Assessments.
vi) The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy.
vii)WOCBP must agree to follow instructions for method(s) of contraception defined in 
Appendix 4 and as described below and included in the informed consent form.
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viii)
WOCBP are permitted to use hormonal contraception methods (as described in 
Appendix 4).
ix) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies:
(1) Is not a WOCBP 
OR
(2) Is a WOCBP and using one of the highly effective contraceptive methods as 
described in Appendix 4 for the duration of treatment with study drugs (BMS-
986141, aspirin, ticagrelor) plus at least 5 half-lives of BMS-986141 (9 days, 5 half-
lives of aspirin and ticagrelor are shorter than 9 days)
b) Male Participants 
i)
Males, ages 18 to 75 years, inclusive.
ii) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception defined in Appendix 4 and as described below.
iii) Azoospermic males are exempt from contraceptive requirements.
iv) No additional contraceptive measures are required to be used.
6.2
Exclusion Criteria
1) Medical Conditions - All Participants
a) Women who are breastfeeding
b) Acute coronary syndrome or coronary revascularisation within 3 months of study treatment 
administration
c) Coagulation disorders (including any abnormal bleeding or blood dyscrasias), anaemia, or 
renal or hepatic insufficiency
d) Current or recent bleeding, including, but not limited to, epistaxis, gastrointestinal, or 
urogenital bleeding
e) Acute illness, including a common cold, within 7 days of study treatment administration 
or any other significant acute or chronic medical illness
f)
Active malignancy (excluding localized skin cancer)
g) Current or recent (within 3 months of study drug administration) gastrointestinal disease 
that could impact upon the absorption of study treatment
h) Any gastrointestinal surgery that could impact upon the absorption of study treatment
i)
Any major or traumatic surgery within 12 weeks of screening
j)
Donation of blood to a blood bank or in a clinical study (except a screening visit) within 
4 weeks of study treatment administration (within 2 weeks for plasma only)
k) Blood transfusion within 4 weeks of study treatment administration
l)
Inability to tolerate oral medication
m) Inability to be venipunctured and/or tolerate venous access
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n) Recent (within 5 years of study treatment administration) drug or alcohol abuse as defined 
in Diagnostic and Statistical Manual of Mental Disorders (4th Edition), Diagnostic Criteria 
for Drug and Alcohol Abuse (Appendix 5)
o) Any other sound medical, psychiatric and/or social reason as determined by the investigator
p) Evidence of active coronavirus disease (COVID-19) infection
2) Medical Conditions - Treatment Arms 1, 2, and 3
a) Participant does not take 7 consecutive days of ticagrelor BID, aspirin, or ticagrelor BID + 
aspirin prior to Day 1
b) Participants who do not currently receive any antiplatelet therapy, or who are currently on 
aspirin alone as their standard of care, will be excluded from Treatment Arm 3 (triple 
therapy)
c) Current or recent uncontrolled hypertension
d) Participants must not have contraindications to any of the study drugs, specifically to 
aspirin or ticagrelor, including, but not limited to history of intracerebral hemorrhage
3) Prior/Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7
Concomitant Therapy
4) Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG, or clinical laboratory determinations beyond what 
is consistent with the target population (participants with coronary artery disease or healthy 
participants)
b) Hematocrit < 35%, hemoglobin < 11 g/dL, or platelet count < lower limit of normal
c) Participants at screening or prior to first dose of study treatment with the following 
abnormal laboratory values, confirmed by repeat
i)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5× upper 
limit of normal (ULN) for participants in Treatment Arms 1, 2, and 3
ii) ALT or AST > ULN for participants in Treatment Arm 4
iii) Total bilirubin > ULN (participants with mild unconjugated hyperbilirubinemia due to 
Gilbert’s syndrome are excluded)
iv) Creatine kinase > 3× ULN
v) aPTT or prothrombin time/INR > ULN
vi) Blood urea nitrogen or creatinine > ULN
d) Any of the following on 12-lead ECG prior to study treatment administration, confirmed 
by repeat
i)
PR 210 msec
ii) QRS 120 msec
iii) QT 500 msec
iv) QT corrected for heart rate using the Fridericia formula (QTcF) 450 msec
e) Positive urine screen for drugs of abuse
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f)
Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or human 
immunodeficiency virus (HIV) type 1 and 2 antibodies
5) Allergies and Adverse Drug Reaction
a) History of allergy to aspirin, ticagrelor, BMS-986141, or related compounds
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
6) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: Under specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included as a participant. Strict conditions apply and Bristol-Myers 
Squibb [BMS] approval is required.)
b) Employee of the investigator or clinical site, or BMS or PPD, with direct involvement in 
the proposed experiment or other experiments under the direction of that investigator or 
clinical site, as well as family members of the employees or the investigator
c) Inability to comply with restrictions as listed in Section 6.3 Lifestyle Restrictions
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
6.3.1
Meals and Dietary Restrictions

Participants are not permitted to consume grapefruit-containing products from 3 days prior to 
the first dose of study treatment until study discharge.

Participants are not permitted to consume broccoli, cauliflower, radishes, turnips, melons 
(excluding watermelon), and raw or uncooked red meat from 3 days prior to the first dose of 
study treatment until clinic discharge.

Participants should not consume more than 350 mg of Vitamin C from 3 days prior to first 
dose of study treatment until clinic discharge.

Participants may not drink water 1 hour before and 1 hour after dosing on Day 1, except as 
required for dosing. Water may be consumed ad libitum at other times.

Standard meals will be served by the clinical site. There are no specific restrictions regarding 
the content of meals and snacks.
6.3.2
Caffeine, Alcohol and Tobacco

Participants are not permitted to consume alcohol-containing beverages from 3 days prior to 
first dose of study treatment until clinic discharge.

Participants are not permitted to consume caffeine-containing products from 3 days prior to 
first dose of study treatment until clinic discharge.

Participants are not permitted to smoke or use other nicotine- or tobacco-containing products 
while at the study site.
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6.3.3
Activity
Participants are to refrain from strenuous exercise, contact sports, and sunbathing from at least 1 
day prior to the first dose until clinic discharge.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, 
to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, as 
applicable, and to respond to queries from regulatory authorities. Minimal information includes 
date of consent, demography, screen failure details, eligibility criteria, and any serious AEs 
(SAEs).
6.4.1
Retesting During Screening or Lead-In Period
Participant Re-enrollment: This study permits the re-enrollment of a participant that has 
discontinued the study as a pretreatment failure (ie, participant has not been treated). If re-enrolled, 
the participant must be re-consented.
Retesting of laboratory parameters and/or other assessments within any single screening or Lead-in 
period will be permitted (in addition to any parameters that require a confirmatory value).
The most current result prior to study allocation is the value by which study inclusion will be 
assessed, as it represents the participant’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 2-11, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant.
7
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device intended to be administered to a study participant according to the study  allocation.
Study 
treatment 
includes 
both 
Investigational 
[Medicinal] 
Product 
(IP/IMP) 
and 
Non-investigational [Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:

BMS-986141 oral tablets at a dose of 4 mg (IP)

Ticagrelor oral tablets at a dose of 90 mg BID (IP)

Aspirin oral tablets at a dose of 75 mg (IP)
An IP, also known as IMP in some regions, is defined as a pharmaceutical form of an active 
substance or placebo being tested or used as a reference in a clinical study, including products 
already with a marketing authorization but used or assembled (formulated or packaged) differently 
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than the authorized form, or used for an unauthorized indication, or when used to gain further 
information about the authorized form.
The study treatments for this study are presented in Table 7-1. Instructions for storage and 
administration will be provided to the investigative site separate from the protocol.
The investigator will source, purchase, and provide sufficient marketed product of ticagrelor 
90-mg tablets and aspirin 75-mg tablets.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-IPs.
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Table 7-1:
Study Treatments for CV006037
Product Description / 
Class and Dosage 
Form
Potency
IP/Non-IMP
Blinded or Open 
Label
Packaging / 
Appearance
Storage Conditions
(per label)
BMS-986141 tablets
4 mg
IP
Open label
Tablets in HDPE 
containers
Refer to labeled 
instructions
Ticagrelora
90 mg
IP
Open label
Tablets in commercial 
packaging
Refer to SmPC
Aspirina
75 mg
IP
Open label
Tablets in commercial 
packaging
Refer to SmPC
a Ticagrelor and aspirin will be sourced by the study investigator and not provided by BMS as local commercial product. Storage should be in accordance with 
the package insert or summary of product characteristics (SmPC).
Abbreviations: HDPE = high-density polyethylene; IP = investigational product; SmPC = summary of product characteristics
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7.1
Treatments Administered
The selection and timing of dose for each participant is as follows:
Table 7.1-1:
Selection and Timing of Dose
Study Treatment
Unit dose 
strength/Dosage level
Dosage formulation
Frequency of Administration
Route of 
Administration
Treatment Arm 1
A
Ticagrelora
90 mg
Twice daily dose on Day 1
Single dose in the morning of 
Day 2
Oral
B
BMS-986141
4 mg
Single dose on Day 1
Oral
Treatment Arm 2
C
Aspirin
75 mg
Single dose on Day 1 and 
Day 2
Oral
D
BMS-986141
4 mg
Single dose on Day 1
Oral
Treatment Arm 3
E
Ticagrelora
90 mg
Twice daily dose on Day 1
Single dose in the morning of 
Day 2
Oral
Aspirin
75 mg
Single dose on Day 1 and 
Day 2
Oral
F
BMS-986141
4 mg
Single dose on Day 1
Oral
Treatment Arm 4
G
BMS-986141
4 mg
Single dose on Day 1
Oral
a The second dose of ticagrelor will be administered approximately 12 hours after the first dose.
In the morning on Day 1 and/or Day 2, each participant will receive a single oral dose of the 
treatment(s) based on their assigned treatment arm. At the time of dosing, water will be 
administered to the participant along with his/her dose of study drug. The dose will be administered 
with a total volume of approximately 240 mL of water. The time of dose administration will be 
called “0” hour.
Restrictions related to food and fluid intake are described in Section 6.3.
7.2
Method of Treatment Assignment
Study treatment will be dispensed at the study visits as listed in Schedule of Activities (Section 2). 
Treatment arms will not be randomized but instead be allocated as open-label at the discretion of 
the Principal Investigator as detailed in Section 5.1.
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Enrolled participants, including those not dosed, will be assigned sequential participant numbers 
starting with 00001 (eg, 00001, 00002, 00003.... 00010). Those enrolled participants meeting 
inclusion and exclusion criteria will be eligible to be dosed.
Participants will not be replaced if they are discontinued from the study secondary to an AE unless 
the AE can be determined to be unrelated to treatment. If a participant is replaced after dosing then 
the replacement participant will be assigned the original participant’s number plus 100. The 
replacement participant will receive the same treatment as the participant being replaced, but a 
new participant number will be assigned to him or her. For example, participant 00004 would be 
replaced by Participant 00104.
7.3
Blinding
This is an open-label study; blinding procedures are not applicable.
Aortic strip analysis will be performed blinded. Aortic strips will be assigned and stored with a 
unique sample number unrelated to the participant number. Aortic strips will be processed by the 
histology department, who are blinded to the study entirely, and analyzed at a later date by an 
operator blinded to the aortic strip linked sample numbers.
7.4
Dosage Modification
Modifications of the dosage schedule may not be made without a written amendment to the 
protocol.
7.5
Preparation/Handling/Storage/Accountability
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study participants. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and contact BMS immediately.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
For study drugs not provided by BMS and obtained commercially by the site, storage should be in 
accordance with the product label.
Further guidance and information for final disposition of unused study treatment are provided in 
Appendix 2 and as specified by the study team.
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7.5.1
Retained Samples for Bioavailability / Bioequivalence / 
Biocomparability
Not applicable.
7.6
Treatment Compliance
Participants may take part in an optional Run-in Period after screening if participants are taking a 
similar antiplatelet drug (eg, clopidogrel), a lower dose of ticagrelor BID, aspirin, or ticagrelor 
BID + aspirin or are not currently taking ticagrelor BID, aspirin, or ticagrelor BID + aspirin as part 
of their standard of care. Participants will receive ticagrelor BID, aspirin, or ticagrelor BID + 
aspirin daily for at least 7 days under the supervision of the investigator prior to Day 1. Participants
will record the timing of each dose and number of tablets taken in a diary. Diaries will be reviewed 
by study site personnel on Day 1. Participants who do not have 100% compliance will not continue 
in the study.
Study drug will be administered in the clinical facility. After administration of study treatments, 
an examination of the oral cavity is required to verify that a participant has swallowed the oral 
solution or tablet. The participant should drink the entire aliquot of water given to swallow the oral 
solution or tablet. 
The examiner should have the participant open the mouth and stick out the tongue far enough to 
permit visualization of the posterior most part of the tongue. A light source should be used to
ensure complete visualization, and in some cases, it may be necessary to use a tongue blade. The 
participant should be directed to move the tongue up and then from side to side. It may be necessary 
to use a tongue blade to move the tongue far enough to permit full visualization of the area under 
the tongue. The tongue blade should then be used to inspect the sulcus between the gums and the 
inner cheeks in all 4 quadrants. The participant should then be asked to lift the upper and lower 
lips to permit visualization of the sulcus between the inner lip and the gums.
7.7
Concomitant Therapy
7.7.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications taken prior to study drug administration in the study are 
described below. Medications taken within 4 weeks prior to BMS-986141 administration must be 
recorded on the case report form (CRF). Any SARS-CoV-2 vaccination should be recorded.
1) Prior exposure to BMS-986141.
2) Exposure to any IP or placebo within 4 weeks of study treatment administration.
3) Exposure to any biologics within 5× T-HALF of study treatment administration.
4) Exposure to any vaccines within 7 days of study treatment administration. If participants are 
receiving the SARS-CoV-2 vaccine as a 2-dose series, the entire series should be completed 
before enrollment.
5) Use of any other drugs, including over-the-counter medications and herbal preparations, within 
1 week prior to study treatment administration.
6) Use of any known strong CYP3A4 inhibitors within 2 weeks prior to study treatment 
administration or during the study (Appendix 6).
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7) Use of anticoagulant therapy within 1 week of screening.
8) Use of any agent, nonsteroidal anti-inflammatory compounds, anticoagulants, fish oil capsules, 
and gingko, which are known to increase the potential for bleeding within 2 weeks prior to 
study treatment administration.
9) Use of St John’s Wort within 4 weeks prior to study treatment administration and during the 
study.
10) For participants in Treatment Arm 4, use of dual antiplatelet therapy within 2 weeks of 
screening.
Participants in Treatment Arms 1, 2, and 3 may receive treatment with medications necessary for 
maintaining the clinical status of their condition as described in Inclusion Criteria. Background 
therapy may determine eligibility and treatment arm.
No concomitant medications (prescription, over-the-counter, or herbal) are to be administered 
during study unless they are prescribed for treatment of specific clinical events. All medications 
should be approved by the PPD Medical Monitor and BMS Clinical Monitor prior to 
administration unless it is an emergent situation. Any concomitant therapies must be recorded on 
the CRF.
7.8
Treatment After the End of the Study
At the end of the study, BMS will not continue to provide BMS supplied study treatment to 
participants/investigators unless BMS chooses to extend the study. The investigator should ensure 
that the participant receives appropriate standard of care to treat the condition under study.
7.9
Return to Previous Therapy
Participants in Treatment Arms 1-3 upon completion of the study, may then resume their prior 
anti-platelet therapeutics such as aspirin, ticagrelor or clopidogrel, as per recommendations of the 
Principal Investigator, according to Good Clinical Practice, and consistent with current standard 
of care.
A follow-up telephone call from the site to each participant shall be conducted to ensure clarity on 
participant resumption of any prior medications, including prior anti-platelet therapeutics, and to 
ensure participant safety.
8
DISCONTINUATION CRITERIA
8.1
Discontinuation from Study Treatment
Participants MUST discontinue IP (and non-IP at the discretion of the investigator) for any of the 
following reasons:

Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information
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
Any clinical AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant

Termination of the study by BMS

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply and 
BMS approval is required.)

Inability to comply with the protocol

Discretion of the investigator

Overt bleeding producing a hemoglobin decrease ≥ 2 g/dL in 24 hours, confirmed by repeat

Any overt bleeding deemed by the investigator to necessitate discontinuation of study 
medication

QTcF interval > 500 msec or increase in QTc interval of > 60 msec from baseline (confirmed 
by repeat ECG)

Medical or surgical treatment for bleeding beyond the application of pressure or cold 
compresses

Need for treatment with a strong CYP3A4 inhibitor
Discontinuation of the study treatment for abnormal liver tests should be considered by the 
investigator when a participant meets one of the conditions outlined in Section 9.2.7 or if the 
investigator believes that it is in best interest of the participant.
Refer to the Schedule of Activities (Section 2) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that can be completed
In the case of pregnancy, the investigator must immediately, within 24 hours of awareness of the 
pregnancy, notify the BMS Medical Monitor/designee of this event. In most cases, the study 
treatment will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for participant safety). Refer to Section 9.2.5 Pregnancy. 
All participants who discontinue study treatment should comply with protocol-specified follow-up 
procedures as outlined in Section 2. The only exception to this requirement is when a participant 
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page.
8.1.1
Post Study Treatment Study Follow-up
Participants who discontinue study treatment may continue to be followed.
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8.1.2
Stopping Rules
Dosing for all participants will be stopped until safety information can be reviewed if any one of 
the following criteria is met and confirmed by repeat test as appropriate (a repeat draw must be 
performed within 24 hours):

Two or more participants have a related SAE

Two or more participants have an AE at severe intensity

One participant with a clinically significant bleeding event (eg, CNS, severe epistaxis, severe 
hematuria, hematemesis, or GI bleeding) defined as a hemoglobin drop of ≥3 grams, a 
reduction hematocrit by ≥30%, or requiring blood transfusion or hemodynamic support to
maintain systolic blood pressures

One participant with serum blood urea nitrogen or creatinine > 2× ULN (confirmed by repeat)

Two or more participants have QTcF > 500 msec (confirmed by repeat ECG)

Two or more participants have AST and/or ALT > 5× ULN (confirmed by repeat)

One participant has AST and/or ALT > 3× ULN AND total bilirubin > 2.0× ULN (confirmed 
by repeat)

Two or more participants have a total bilirubin > 3.0× ULN (confirmed by repeat)

One participant has ALT or AST > 3× ULN (confirmed by repeat) with the appearance or 
worsening of symptoms felt by the investigator to be potentially related to hepatic injury, such 
as fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or 
eosinophilia

Two or more participants with an SAE or an AE of serious degree occurs in any treatment arm 
of the study, either within the same group or in different study groups, further dosing in the 
study for all groups will be paused until a full safety review can be conducted, and make a 
determination whether or not further dosing in this group or in any other study group shall 
proceed
The Sponsor and investigator may decide to halt dosing for reasons not defined above, including 
but not limited to, observing a single SAE in individual participants and/or observing trends during 
the study. If any of the listed stopping rules are met on review of the data, dosing will not be 
resumed.
If any of the above criteria are met, the study will be put on hold and all safety data available across 
the study will be evaluated to estimate the risk of proceeding. Upon conclusion of this in-depth 
safety review, one of the following recommendations will be made:

To continue with the study as planned (ie, there are no clinically significant safety concerns);

To continue with the study by repeating the current treatment arm in more participants. Any 
restart after the stopping rules have been met will require prior approval of a substantial 
amendment providing justification for the restart;

To continue with a modified dose regimen deemed necessary by safety, tolerability, or PK
analysis;
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
To terminate the study.
8.2
Discontinuation from the Study
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol-specified follow-up procedures. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 

Participants should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.

The withdrawal of consent should be explained in detail in the medical records by the 
investigator, as to whether the withdrawal is from further treatment with study treatment only 
or also from study procedures and/or post treatment study follow-up, and entered on the 
appropriate CRF page.

In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.

If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.3
Lost to Follow-Up

All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of three
documented phone calls, faxes, or emails as well as lack of response by participant to one 
registered mail letter. All attempts should be documented in the participant’s medical records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the participant’s informed consent, then the investigator may use a 
Sponsor retained third-party representative to assist site staff with obtaining participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.

If after all attempts, the participant remains lost to follow-up, then the last known alive date as 
determined by the investigator should be reported and documented in the participant’s medical 
records.
9
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and timing are summarized in the Schedule of Activities (Section 2). 
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
Protocol waivers or exemptions are not allowed.

All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment.

Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before study allocation. The investigator will maintain 
a screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in the Schedule of Activities.
9.1
Efficacy Assessments
Not applicable.
9.1.1
Imaging Assessment for the Study
At the sponsor’s discretion, scans may be collected for review.
This is not applicable for this study.
9.2
Adverse Events
The definitions of an AE or SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study. 
Contacts for SAE reporting are specified in Appendix 3
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
Appendix 1 in the IB (BMS-986141) and Section 4.8 in the Summary of Product Characteristics 
(aspirin and ticagrelor) represent the Reference Safety Information, and they are used to determine 
expectedness of SAEs for expedited reporting.
All SAEs must be collected from the time of signing the consent, including those thought to be
associated with protocol-specified procedures and within 30 days of discontinuation of dosing.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure, (eg, a follow-up skin biopsy).
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
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the CRF module.

All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 

The investigator will submit any updated SAE data to the sponsor or designee within 24 hours
of updated information being available.
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the investigator must promptly notify the sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3.
9.2.2
Method of Detecting AEs and SAEs
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a participant. Care should be taken not to introduce bias when 
collecting AE and/or SAEs. Inquiry about specific AEs should be guided by clinical judgement in 
the context of known AEs, when appropriate for the program or protocol.
9.2.3
Follow-up of AEs and SAEs

Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study treatment as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.
All SAEs will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in Appendix 3.
9.2.4
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
product under clinical investigation are met.

An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements.
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Sponsor or designee will be reporting adverse events to regulatory authorities and ethics 
committees according to local applicable laws including European Directive 2001/20/EC and FDA 
Code of Federal Regulations 21 CFR Parts 312 and 320. A SUSAR (Suspected, Unexpected 
Serious Adverse Reaction) is a subset of SAEs and will be reported to the appropriate regulatory 
authorities and investigators following local and global guidelines and requirements.
9.2.5
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least for
5 half-lives (5 days) plus 30 days (duration of ovulatory cycle), for a total of 35 days after study 
product administration, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form to BMS 
Designee within 24 hours of awareness of the event and in accordance with SAE reporting 
procedures described in Appendix 3.
If the investigator determines a possible favorable benefit/risk ratio that warrants continuation of 
study treatment, or re-initiation of study treatment, a discussion between the investigator and the 
BMS Medical Monitor/designee must occur. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information, must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor or designee. In order for Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an informed consent form for 
disclosure of this information. Information on this pregnancy will be collected on the Pregnancy 
Surveillance Form.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted

Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value).
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9.2.7
Potential Drug Induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section 9.2 and Appendix 3 for reporting 
details).
Potential DILI is defined as: 
1) ALT or AST elevation > 3× ULN
AND
2) Total bilirubin > 2× ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3) No other immediately apparent possible causes of aminotransferase elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic.
9.2.8
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, x-ray 
filming, any other potential safety assessment required or not required by protocol should also be 
recorded as a nonserious or SAE, as appropriate, and reported accordingly.
9.3
Overdose
For this study, any dose of BMS-986141 greater than 4 mg and any dose of aspirin greater than 
75 mg within a 24-hour time period will be considered an overdose. As the standard of care for 
ticagrelor is 90 mg given BID, any dose of ticagrelor greater than 180 mg within a 24-hour time 
period will be considered an overdose.
9.4
Safety
Planned time points for all safety assessments are listed in the Schedule of Activities (Section 2).
9.4.1
Physical Examinations
Refer to Schedule of Activities (Section 2).
9.4.1.1
Medical Photography
Starting on Day 1, standard baseline photographs of any area with clinical findings will be taken
at the discretion of the Principle Investigator. If there are any changes with the affected areas or 
new clinical findings, additional photographs will be obtained. Photographs will not be needed if 
there is no clinical finding or no change in the affected areas.
9.4.2
Vital signs
Refer to Schedule of Activities (Section 2).
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9.4.3
Electrocardiograms
Refer to Schedule of Activities (Section 2).
9.4.4
Clinical Safety Laboratory Assessments

Investigators must document their review of each laboratory safety report.

A local laboratory will perform the analyses and will provide reference ranges for these tests.

Results of clinical laboratory tests performed on Day 1 must be available prior to BMS-986141 
dosing.
Hematology
Red blood cells
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Chemistry
AST
ALT
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase 
Creatinine
Blood urea nitrogen
Uric acid 
Fasting glucose
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Coagulation
INR
aPTT
Prothrombin time
Platelet count
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive 
on the dipstick
Serology
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Serum for hepatitis C antibody, hepatitis B surface antigen, HIV-1 and -2 antibodies
(screening only). See Appendix 7 for hepatitis B serologic test results interpretation.
Other Analyses
Test for drugs of abuse and alcohol (urine or serum) (screening and Day 1)
Pregnancy test (WOCBP only: screening, predose, clinic discharge)
Follicle-stimulating hormone (postmenopausal women only; screening) 
9.4.5
Imaging Safety Assessment
Not applicable.
9.5
Pharmacokinetics
Pharmacokinetic characteristics of BMS-986141, metabolite BMT-162856, ASA, salicylic acid, 
and ticagrelor will be observed from plasma concentration versus time data. Potential correlation 
between drug exposures and thrombus formation in an ex vivo porcine aortic thrombosis chamber 
and other biomarkers/PD markers will be explored. The PK samples being collected will provide 
concentrations near Tmax.
Table 9.5-1 (Treatment Arm 1), Table 9.5-2 (Treatment Arm 2), Table 9.5-3 (Treatment Arm 3), 
and Table 9.5-4 (Treatment Arm 4) list the sample schedule to be following for the PK assessments 
of BMS-986141, ticagrelor, and ASA.
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Table 9.5-1:
Pharmacokinetic Sampling Schedule for BMS-986141 and 
Ticagrelor (Treatment Arm 1)
Study Day of 
Sample Collection
Event
Time
(Relative To 
BMS-986141
Dose)Hour: Min
BMS-986141 and 
BMT-162856
Blood Sample for 
Plasma PK Profiling
Ticagrelor
Blood Sample for 
Plasma PK Profiling
1
predosea
-02:00
X
X
1
02:00
X
X
2
24:00
X
X
a The predose sample should be collected within 2 hours prior to BMS-986141 administration.
Abbreviation: PK = pharmacokinetic
Table 9.5-2:
Pharmacokinetic Sampling Schedule for BMS-986141 and 
Acetylsalicylic Acid (Treatment Arm 2)
Study Day of 
Sample Collection
Event
Time
(Relative To 
BMS-986141
Dose)Hour: Min
BMS-986141 and 
BMT-162856
Blood Sample for 
Plasma PK Profiling
Acetylsalicylic Acid 
and Salicylic Acid
Blood Sample for 
Plasma PK Profiling
1
predosea
-02:00
X
X
1
02:00
X
X
2
24:00
X
X
a The predose sample should be collected within 2 hours prior to BMS-986141 administration.
Abbreviation: PK = pharmacokinetic
Table 9.5-3:
Pharmacokinetic Sampling Schedule for BMS-986141, Ticagrelor, 
and Acetylsalicylic Acid (Treatment Arm 3)
Study Day of 
Sample Collection
Event
Time
(Relative To 
BMS-986141
Dose)Hour: 
Min
BMS-986141 
and 
BMT-162856
Blood Sample 
for Plasma PK 
Profiling
Ticagrelor
Blood Sample 
for Plasma PK 
Profiling
Acetylsalicylic 
Acid and 
Salicylic Acid
Blood Sample 
for Plasma PK 
Profiling
1
predosea
-02:00
X
X
X
1
02:00
X
X
X
2
24:00
X
X
X
a The predose sample should be collected within 2 hours prior to BMS-986141 administration.
Abbreviation: PK = pharmacokinetic
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Table 9.5-4:
Pharmacokinetic Sampling Schedule for BMS-986141 (Treatment 
Arm 4)
Study Day of Sample 
Collection
Event
Time
(Relative To 
BMS-986141
Dose)Hour: Min
BMS-986141 and 
BMT-162856
Blood Sample for 
Plasma PK Profiling
1
predose
00:00
X
1
02:00
X
2
24:00
X
Abbreviation: PK = pharmacokinetic
The plasma samples will be analyzed for BMS-986141, ASA, salicylic acid, and ticagrelor by 
validated liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) assays. 
BMT-162856, a metabolite of BMS-986141, will be analyzed by a qualified LC-MS/MS assay. In 
addition, plasma samples will be archived for potential metabolite analysis, if the need arises and 
to the extent possible.
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the procedure manual.
9.6
Pharmacodynamics
Refer to Section 9.8.
 
 
 
 
 
9.8
Biomarkers
Thrombus formation will be determined using the Badimon chamber. Venous blood will be 
collected from study participants through a cannula set attached to extension tubing. The tubing 
will be connected to a series of 3 perfusion chambers containing porcine aorta as a thrombogenic 
surface. A pump placed distal to the chambers will maintain unidirectional flow at a rate of 
10 mL/min. The rheologic conditions in the first chamber stimulate those of patent arteries (low 
shear rate, approximately 212 s-1), and those in the second and third chambers simulate those of 
stenosed arteries (high shear rate, approximately 1690 s-1). Each perfusion study will last for 
5 minutes. Immediately after each perfusion, porcine strips with thrombus attached will be 
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removed and fixed, and total thrombus area will be assessed by morphometrical analysis. 
Aortic strip analysis will be performed blinded. Aortic strips will be assigned and stored with a 
unique sample number unrelated to the participant number. Aortic stripes are then processed by 
the histology department, who are blinded to the study entirely, and analyzed at a later date by an 
operator blinded to the aortic strip linked sample numbers. Sample linkage will be kept securely 
in the study site.
Circulating biomarker assessment for this chamber study focuses primarily on PD biomarkers. 
 
 
 
 
 
 
In addition, serum samples will be collected for assessment of SARS-CoV-2 serology.
Blood will be drawn at the times indicated in Table 9.8-1 and Table 9.8-2. Further details of blood 
collection and processing will be provided to the site in the procedure manual. 
Table 9.8-1:
Biomarker Sampling Schedule - Treatment Arms 1, 2, and 3
Study Day 
of Sample 
Collection
Event
Time
(Relative To 
BMS-986141 
Dose)
Hour:Min
 
 
 
 
 
 
 
 
 
Serum for 
SARS-CoV-2 
serology
1
predose
-02:00
X
1
02:00
2
24:00
Abbreviations: 
 
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Table 9.8-2:
Biomarker Sampling Schedule - Treatment Arm 4
Study Day 
of Sample 
Collection
Event
Time
(Relative To 
BMS-
986141
Dose)
Hour:Min
 
 
 
 
 
 
 
 
 
 
Serum for 
SARS-CoV-2 
serology
1
predose
00:00
X
1
02:00
2
24:00
Abbreviations: 
 
9.8.1
Additional Research Collection
This protocol will include residual sample storage.
For All US Sites:
Not applicable.
For non-US Sites
Additional research is optional for all study participants, except where retention and/or collection 
is prohibited by local laws or regulations, ethics committees, or institutional requirements.
This collection for additional research is intended to expand the translational R&D capability at 
Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our 
understanding of disease and options for treatment. It may also be used to support health authority 
requests for analysis, and advancement of pharmacodiagnostic development to better target drugs 
to the right patients.  This may also include genetic/genomic exploration aimed at exploring disease 
pathways, progression and response to treatment etc. 
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study sponsor’s senior leaders in Research and Development (or designee) to 
ensure the research supports appropriate and well-defined scientific research activities.
 biomarker, and 
 (see Table 9.8.1-1) will also 
be retained for additional research purposes.
Samples kept for future research will be stored at the 
  
 or 
an independent, BMS-approved storage vendor.
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than fifteen (15) 
years after the end of the study or the maximum allowed by applicable law.
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Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
Table 9.8.1-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time Points for Which Residual Samples Will be Retained
Plasma PK
All
Whole blood/DNA
All
Plasma serum biomarkers
All
Abbreviation: PK = pharmacokinetic
9.8.2
Other Assessments
Not applicable.
9.9
Health Economics OR Medical Resource Utilization and Health 
Economics
Health Economics/Medical Resource Utilization and Health Economics parameters will not be 
evaluated in this study.
10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination 
The sample size for this study is not based on statistical power, but based on consideration of the 
precision of the estimate of the effect of BMS-986141 alone and as add on to aspirin, ticagrelor, 
or the aspirin/ticagrelor combination, on thrombus formation in an ex vivo porcine aortic 
thrombosis chamber model as compared to pretreatment.
The half-width of the 95% CI of the change from baseline in thrombus area on the log scale after 
administration of BMS-986141 will be 0.146 or 0.188 if there are 15 or 10 participants per arm, 
respectively. This calculation assumes that the thrombus area is log-normally distributed and the 
change from baseline on the log scale has a standard deviation of 0.263 as observed in CV004-007.
The following table provides examples of 95% CIs of the true percent reduction in thrombus area
after administration of BMS-986141, assuming the true percent reduction (percent decrease from 
baseline) is 15%, 20%, or 30%, and the sample size is 15 per arm or 10 per arm.
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Sample Size per 
Arm
True Reduction 
from Baseline
Change from Baseline on Log 
Scale (95% CI)
Geometric Mean Ratio to 
Baseline (95% CI)
15
15%
-0.163 (-0.309, -0.017)
0.85 (0.73, 0.98)
15
20%
-0.223 (-0.369, -0.077)
0.80 (0.69, 0.93)
15
30%
-0.357 (-0.503, -0.211)
0.70 (0.60, 0.81)
10
30%
-0.357 (-0.545, -0.169)
0.70 (0.58, 0.84)
Approximately 55 participants (15 participants in Treatment Arms 1, 2, and 3, and 10 participants 
in Treatment Arm 4) are planned to be dosed with BMS-986141.
10.2
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign informed consent
Treated
The Treated Population is a subset of the Enrolled Population
including all participants who received BMS-986141.
Pharmacokinetic
The PK Population is a subset of the Treated Population. The PK
Population includes all participants who received BMS-986141
and had any available concentration-time data
Biomarker
The Biomarker Population is a subset of the Treated Population. 
The Biomarker Population includes all participants who received 
BMS-986141 and had any available biomarker data.
10.3
Statistical Analyses
The statistical analysis plan will be developed and finalized before database lock and will describe 
the selection of participants to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. Below is a summary of planned statistical analyses of the 
primary and secondary endpoints.
10.3.1
Efficacy Analyses
Not applicable.
10.3.2
Safety Analyses
All safety analyses will be performed on the Treated Population.
Endpoint
Statistical Analysis Methods
Secondary:
AEs, clinical 
laboratory 
Descriptive summaries will be presented for continuous variables using number 
of participants (N), mean, standard deviation, median, minimum, and 
maximum. Descriptive summaries for categorical variables will utilize counts 
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values, vital 
signs, ECGs, 
or other safety 
biomarkers
and percentages. All recorded AEs will be listed and tabulated by system organ 
class, preferred term, treatment arm, and treatment. Vital signs, ECGs, and 
clinical laboratory test results will be listed and summarized by planned time 
point, treatment arm, and treatment. Marked abnormal clinical laboratory test 
results will be summarized by treatment arm and treatment. Any significant 
physical examination findings will be listed. Electrocardiogram readings will 
be summarized by planned time point, treatment arm, and treatment, and 
investigator-identified abnormalities, if present, will be listed. 
10.3.3
Other Analyses 
Endpoint
Statistical Analysis Methods
Primary:
Change from 
baseline in 
thrombus area 
(post-treatment 
with 
BMS-986141 
vs. 
pretreatment)
An analysis of variance will be performed on the natural logarithm (ln)-
transformed thrombus area using general linear mixed effects models 
separately by shear rates (Low or High) with perfusion run (baseline, 2 hours, 
and 24 hours) as fixed effects and participant as a random effect. A 
supplemental analysis of variance will be performed on the natural 
ln-transformed thrombus area using general linear mixed effects models 
separately by shear rates (Low or High) with treatment arm, perfusion run 
(baseline, 2 hours, and 24 hours) as fixed effects and participant as a random 
effect. Means, mean differences from baseline, and the 95% CI of mean 
differences on the log scale will be estimated from the models and be 
exponentiated to express the results as geometric means, geometric mean 
ratios to baseline, and the 95% CI of geometric mean ratios on the original 
scale. All thrombosis chamber endpoints will be listed, plotted and 
summarized by treatment arm, shear rate, and perfusion run.
 
 Summary statistics for each of the biomarkers and their corresponding percent 
changes from baseline will be tabulated by treatment arm, shear rate, and perfusion run. Plots of 
mean values of biomarkers, as well as geometric mean percent changes from baseline versus shear 
rate and perfusion run will be provided for each treatment arm. Potential correlation between
BMS-986141 exposure and thrombus formation in an ex vivo porcine aortic thrombosis chamber
and other biomarkers/PD markers will be explored.
Summary statistics for PK concentrations of BMS-986141, metabolite BMT-162856, ASA, 
salicylic acid, and ticagrelor will be tabulated.
 
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10.3.4
Interim Analyses
Not applicable.
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11
REFERENCES
1
Wang Y, Johnston SC, Bath PM, et al. Acute dual antiplatelet therapy for minor ischaemic 
stroke or transient ischaemic attack. BMJ. 2019;364:l895.
2
http://www.world-heart-federation.org/cardiovascular-health/stroke/
3
Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2015 update: 
A report from the American Heart Association. Circulation. 2015;131:e29-e322.
4
Sandercock PAG, Counsell C, Tseng MC, et al. Oral antiplatelet therapy for acute ischaemic 
stroke. 
Cochrane 
Database 
of 
Syst 
Rev.
2014: 
CD000029. 
DOI: 
10.1002/14651858.CD000029.pub3.
5
Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient 
ischemic attack. N Engl J Med. 2013;369(1):11-9.
6
Zwaginga JJ, Sakariassen KS, Nash G. et al. Flow-based assays for global assessment of 
haemostasis. Part 2: current methods and considerations for the future. Thromb Haemost.
2006;4(12):2716-7.
7
Philips DR, Coniley PB, Shinha U, et al. Therapeutic approaches in arterial thrombosis. J. 
Thromb Haemost. 2005;3(8):1577-89.
8
Shimbo D, Osende J, Chen J, et al. Antithrombotic effects of DX-9065a, a direct factor Xa 
inhibitor: a comparative study in humans versus low molecular weight heparin. Thromb 
Haemost 2002;88(5):773-8.
9
André P, LaRocca T, Delaney SM, et al. Anticoagulants (thrombin inhibitors) and aspirin 
synergize 
with 
P2Y12 
receptor 
antagonism 
in 
thrombosis. 
Circulation. 
2003;108(21):2697-703.
10 Roald HE, Barstad MR, Kierulf P, et.al. Clopidogrel - a platelet inhibitor which inhibits 
thrombogenesis in non-anticoagulated human blood independently of the blood flow 
conditions. Thromb Haemost 1994;71(5):655-62.
11 Cadroy Y, Thalamas C, Sakariassen J, et al. Superior efficacy of clopidogrel plus 
acetylsalicylic acid compared with extended-release dipyridamole plus acetylsalicylic acid in 
preventing arterial thrombogenesis in healthy volunteers. Thromb Res. 2005;116(4):293-300.
12 Sakariassen KS, Turitto VT, Baumgartner HR. Recollections of the development of flow 
devices for studying mechanism of homeostasis and thrombosis in flowing whole blood. J 
Thromb Haemost. 2004;2(10):1681-90.
13 Coughlin 
SR. 
Thrombin 
signaling 
and 
protease-activated 
receptors. 
Nature.
2000;407(6801):258-64.
14 Covic L, Gresser AL, Kuliopulos A. Biphasic kinetics of activation and signaling for PAR1 
and PAR4 thrombin receptors in platelets. Biochemistry. 2000;39(18):5458-67.
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15 Ishii K, Hein L, Kobilka B, et al. Kinetics of thrombin receptor cleavage on intact cells. 
Relation to signaling. J Biol  Chem. 1993;268(13):9780-6.
16 Mazharian A, Roger S, Berrou E, et al. Protease-activating receptor-4 induces full platelet 
spreading on a fibrinogen matrix: involvement of ERK2 and p38 and Ca2+ mobilization. J 
Biol Chem. 2007;282(8):5478-87.
17 Covic L, Singh C, Smith H, et al. Role of the PAR4 thrombin receptor in stabilizing 
platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome. 
Thromb Haemost. 2002;87(4):722-7.
18 Gresele P, Falcinelli E, Momi S. Potentiation and priming of platelet activation: a potential 
target for antiplatelet therapy. Trends Pharmacol Sci. 2008;29(7):352-60.
19 Brass LF, Zhu L, Stalker TJ. Minding the gaps to promote thrombus growth and stability. J 
Clin Invest. 2005;115:3385-92.
20 BMS-986141, Bristol-Myers Squibb Investigator Brochure Version 04, 09-June-2017. BMS 
Document Control No. 930079878.
21 BMS-986141: Preclinical inhibition of  platelet aggregation. (Study CV00003). Bristol-Myers 
Squibb Company; 2014. Document Control No. 930074776.
22 Nonclinical evaluation of the pharmacokinetics and metabolism of BMS-986141. (Study 
NCPK131). Bristol-Myers Squibb Company; 2014. Document Control No. 930078641.
23 In vitro characterization of absorption properties of BMS-986141 in Caco-2 bidirectional 
permeability assay (Study NCPK240). Bristol-Myers Squibb Company; 2015. Document 
Control No. 930090233.
24 In vitro characterization of absorption, distribution, metabolism, and elimination properties of 
BMT-162856, a metabolite of BMS-986141 (Study NCPK127). Bristol-Myers Squibb 
Company; 2015. Document Control No. 930078359.
25 UDM-003183: Four-day oral exploratory toxicokinetic and tolerability study in rats (Study 
DT13108). Bristol-Myers Squibb Company; 2014. Document Control No. 930076103.
26 Wong P, Seiffert D, Bird JE, et al. Blockade of protease-activated receptor-4 (PAR4) provides 
robust antithrombotic activity with low bleeding. Sci Transl Med. 2017;9(371):eaaf5294.
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
ADP
adenosine diphosphate
AE
adverse event
ALT
alanine aminotransferase
AP
agonist peptide
aPTT
activated partial thromboplastin time
ASA
acetylsalicylic acid
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC(0-24)
area under the concentration-time curve from time zero to 24 hours after 
dose
AUC(TAU)
area under the concentration-time curve over the dosing interval
BID
bis in die, twice daily
BMI
body mass index
BMS
Bristol-Myers Squibb
CFR
Code of Federal Regulations 
CI
confidence interval
CLTp
total plasma clearance
Cmax
maximum observed concentration
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form, paper or electronic
CYP
cytochrome P450
DILI
drug-induced liver injury
DNA
deoxyribonucleic acid
EC50
concentration required for 50% efficacy
EC80
concentration that gives 80% of Emax
ECAT
cyno-electrically-mediated carotid arterial thrombosis
ECG
electrocardiogram
F
oral bioavailability
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Term
Definition
HIV
human immunodeficiency virus
IB
investigator’s brochure
IC50
concentration at which 50% inhibition observed
IEC
Independent Ethics Committee
IMP
investigational medicinal products
INR
international normalized ratio
IP
investigational product
IRB
institutional review board
LC-MS/MS
liquid chromatography mass spectrometry/mass spectrometry
PAR1
protease-activated receptor 1
PAR2
protease-activated receptor 2
PAR4
protease-activated receptor 4
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PMA
platelet-monocytes aggregates
QTcF
QT corrected for HR using the Fridericia formula
SAE
serious adverse event
sCD40L
soluble CD40 ligand
SDD
spray-dried dispersion
sP-selectin
soluble platelet selectin
SUSAR
suspected, unexpected serious adverse reaction
T-HALF
Half-life
TIA
transient ischemic attack
Tmax
time of maximum observed concentration
ULN
upper limit of normal
Vss
volume of distribution at steady state
vWF
von Willebrand factor
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the CRF is intended to refer to a person 
(Participant) who has consented to participate in the clinical research study.
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:

Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines Good Clinical Practice (GCP), 

as defined by the International Council on Harmonisation (ICH)

in accordance with the ethical principles underlying European Union Directive 2001/20/EC

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 

applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to 
affect, to a significant degree one or more of the following:  (1) the physical, safety or mental 
integrity of one or more subjects/participants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, participant recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects/participants. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure or 
product labeling information to be provided to subjects/participants and any updates. 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
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COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects/participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as soon
as possible to:

IRB/IEC

Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
subjects/participants currently enrolled in the study if they are affected by the amendment; and (3) 
the new form must be used to obtain consent from new subjects/participants prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
FINANCIAL DISCLOSURE
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that subjects/participants are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer 
to participate. 
In situations where consent cannot be given by subjects/participants, their legally acceptable 
representatives (as per country guidelines) are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which the participant 
volunteers to participate. 
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample
informed consent form which will include all elements required by ICH, GCP and applicable
regulatory requirements. The sample informed consent form will adhere to the ethical principles 
that have their origin in the Declaration of Helsinki.
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Investigators must:

Provide a copy of the consent form and written information about the study in the language in 
which the participant is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 

Allow time necessary for participant or participant's legally acceptable representative to 
inquire about the details of the study.

Obtain an informed consent signed and personally dated by the participant or the participant's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 

Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects/participants, prior to the beginning of 
the study, and after any revisions are completed for new information.
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant.
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects’/participants’ signed ICF and, in the US, the subjects’/participants’ signed HIPAA 
Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
The rights, safety, and well-being of the study subjects/participants are the most important 
considerations and should prevail over interests of science and society.
SOURCE DOCUMENTS
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event tracking/reporting, protocol required assessments, and/or drug accountability 
records).
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When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
STUDY TREATMENT RECORDS
Records for study treatments BMS-986141, ticagrelor, and aspirin (whether supplied by BMS, its 
vendors, or the site) must substantiate study treatment integrity and traceability from receipt, 
preparation, administration, and through destruction or return. Records must be made available for 
review at the request of BMS/designee or a Health Authority.
If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each 
participant, including unique participant
identifiers

amount transferred to another area/site for 
dispensing or storage

nonstudy disposition (eg, lost, wasted) 

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 

dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form.
Sourced by site, and not supplied by 
BMS or its vendors (examples include IP 
sourced 
from 
the 
sites 
stock or 
commercial supply, or a specialty 
pharmacy)
The investigator or designee accepts responsibility 
for documenting traceability and study treatment
integrity in accordance with requirements applicable 
under law and the SOPs/standards of the sourcing 
pharmacy.
BMS or designee will provide forms to facilitate inventory control if the investigational site does
not have an established system that meets these requirements.
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CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules in accordance with the applicable regulatory 
requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user 
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals
MONITORING
Sponsor or designee representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable.
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee.
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RECORDS RETENTION
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site. 
If..
Then
Study treatments supplied by BMS (including 
its vendors
Any unused study treatments supplied by BMS 
can only be destroyed after being inspected and 
reconciled by the responsible Study Monitor 
unless study treatments containers must be 
immediately destroyed as required for safety, 
or to meet local regulations (eg, cytotoxics or 
biologics).
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or 
commercial 
supply, 
or 
a 
specialty 
pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
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
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
CLINICAL STUDY REPORT
A Signatory Investigator must be selected to sign the clinical study report. 
For this single site protocol, the Principal Investigator for the site will sign the clinical study report.
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTAg) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTAg.
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors.  No public presentation or publication of any interim results may be made by any 
principal investigator, sub-investigator or any other member of the study staff without the prior 
written consent of the Sponsor.  
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights and conclusion); AND
2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
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4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered.  
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW UP AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation participant administered study treatment
and that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis.

Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and 
should specify "intentional overdose" as the verbatim term
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
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SERIOUS ADVERSE EVENTS
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any 
dose:
Results in death
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe)
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below)
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 

a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)

admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols)
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.7 for the definition of potential DILI.) 
Pregnancy and potential drug induced liver injury (DILI) must follow the same transmission timing 
and processes to BMS as used for SAEs (see section 9.2.5 for reporting pregnancies).
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Any component of a study endpoint that is considered related to study therapy should be reported 
as SAE (e.g., death is an endpoint, if death occurred due to anaphylaxis, anaphylaxis must be 
reported).
EVALUATING AES AND SAES
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. (Note: Follow-
up SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
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REPORTING OF SAES TO SPONSOR OR DESIGNEE

SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event.

SAEs must be recorded on the SAE Report Form.

The required method for SAE data reporting is through the eCRF.

The paper SAE Report Form is only intended as a back-up option when the electronic 
data capture (EDC) system is unavailable/not functioning for transmission of the eCRF 
to BMS (or designee).
In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission
When paper forms are used, the original paper forms are to remain on site

Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission 
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP

Premenarchal

Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Postmenopausal female

A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 
years in the absence of other biological or physiological causes. In addition, females under 
the age of 55 years must have a serum follicle stimulating hormone, (FSH) level 
> 40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. 

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
End of Relevant Systemic Exposure

End of relevant systemic exposure is the time point where the IMP or any active major 
metabolites has decreased to a concentration that is no longer considered to be relevant for 
human teratogenicity or fetotoxicity. This should be evaluated in context of safety margins 
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from the no-observed adverse effect level (NOAEL) or the time required for 5 half-lives of the 
IMP to pass.
METHODS OF CONTRACEPTION
One of the highly effective methods of contraception listed below should be continued for a 
minimum of 9 days (5 half-lives of BMS-986141, 5 half-lives of aspirin and ticagrelor are shorter 
than 9 days) post-treatment completion.
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of <1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b 

oral (birth control pills)

intravaginal (vaginal birth control suppositories, rings, creams, gels)

transdermal 

Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy

Progestogen-only hormonal contraception associated with inhibition of ovulation (This 
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol)b 

oral 

injectable 

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol)b

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS) (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol) b,c

Bilateral tubal occlusion

Vasectomized partner 
A vasectomy is a highly effective contraception method provided that the participant is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used.
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
Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant.

Continuous abstinence must begin at least 30 days prior to initiation of study therapy

It is not necessary to use any other method of contraception when complete abstinence is 
elected. 

WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence 

Periodic abstinence (including but not limited to calendar, symptothermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous.  In this case, alternative 
methods of contraception should be utilized. 
c Intrauterine hormone releasing systems are acceptable methods of contraception in the absence of definitive drug 
interaction studies when hormone exposures from intrauterine devices do not alter contraception effectiveness
Unacceptable Methods of Contraception 

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal(coitus interruptus).

Spermicide only

Lactation amenorrhea method (LAM)

Male or female condom with or without spermicide.  Male and female condoms cannot be 
used simultaneously

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal Sponge with spermicide

Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited)
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COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting
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APPENDIX 5
DIAGNOSTIC CRITERIA FOR DRUG AND ALCOHOL ABUSE
The following is taken from DSM-IV:
Diagnostic Criteria for Psychoactive Substance Dependence
A maladaptive pattern of substance use, leading to clinically significant impairment or distress as 
manifested by three (or more) of the following, occurring at any time in the same 12-month period:
1. Tolerance, as defined by either of the following:
a) A need for markedly increased amounts of the substance to achieve intoxication or desired 
effect,
b) Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
a) The characteristic withdrawal syndrome for the substance,
b) The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms.
3. The substance is often taken in larger amounts or over a longer period than was intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A great deal of time is spent in activities necessary to obtain the substance (e.g., visiting 
multiple doctors or driving long distances), use the substance (e.g., chain-smoking) or recover 
from its effects.
6. Important social, occupational or recreational activities are given up or reduced because of 
substance use.
7. The substance use is continued despite knowledge of having a persistent or recurring physical 
or psychological problem that is likely to have been caused or exacerbated by the substance 
(e.g., current cocaine use despite recognition of cocaine-induce depression, or continued 
drinking despite recognition that an ulcer was made worse by alcohol consumption.)
Criteria for Severity of Psychoactive Substance Dependence:
Mild:  Few, if any, symptoms in excess of those required to make the diagnosis, and the symptoms 
result in no more than mild impairment in occupational functioning or in usual social activities or 
relationships with others.
Moderate:  Symptoms or functional impairment between “mild” and “severe”.
Severe:  Many symptoms in excess of those required to make the diagnosis, and the symptoms 
markedly interfere with occupational functioning or with usual social activities or relationships 
with others.
In Partial Remission:  During the past six months, some use of the substance and some symptoms 
of dependence.
In Full Remission:  During the past six months, either no use of the substance, or use of the 
substance and no symptoms of dependence.
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Diagnostic Criteria for Psychoactive Substance Abuse
A. A maladaptive pattern of psychoactive substance use, leading to clinically significant 
impairment or distress as manifested by one (or more) of the following, occurring at any time 
in the same 12-month period:
1. Recurrent substance use resulting in a failure to fulfill major role obligations at work, 
school, or home (e.g., repeated absences or poor work performance related to substance 
use; substance-related absences, suspensions, or expulsions from school, neglect of 
children or household).
2. Recurrent substance use in situations in which it is physically hazardous (e.g., driving an 
automobile or operating a machine when impaired by substance use).
3. Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly 
conduct).
4. Continued substance use despite having persistent or recurrent social or interpersonal 
problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse 
about consequences of intoxication, physical fights).
B. The symptoms have never met the criteria for substance dependence for this class of substance.
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APPENDIX 6
CYP3A4 AND CYP2B6 GUIDANCE
The lists below are not meant to be all inclusive. Please consult individual drug labels for further
information. Additional information is also available at:
https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionsl
abeling/ucm093664.htm
Table 1:
Classification of In Vivo Inhibitors of CYP Enzymes
CYP Enzymes
Strong Inhibitorsa
≥5-fold Increase in AUC or
> 80% Decrease in CL
Moderate Inhibitorsb
≥2 but < 5-fold Increase in
AUC or 50%-80% Decrease
in CL
Weak Inhibitorsc
≥1.25 but < 2-fold Increase in
AUC or
20%-50% Decrease in CL
CYP3A
Boceprevir, clarithromycin,
conivaptan, grapefruit juice,d
indinavir, itraconazole,
ketoconazole,
lopinavir/ritonavir,
mibefradil,e nefazodone,
nelfinavir, posaconazole,
ritonavir, saquinavir,
telaprevir, telithromycin,
voriconazole
Amprenavir, aprepitant,
atazanavir, ciprofloxacin,
darunavir/ritonavir, diltiazem,
erythromycin, fluconazole,
fosamprenavir, grapefruit
juice,d imatinib, verapamil
Alprazolam, amiodarone,
amlodipine, atorvastatin,
bicalutamide, cilostazol,
cimetidine, cyclosporine,
fluoxetine, fluvoxamine,
ginkgo,f goldenseal,f isoniazid,
nilotinib, oral contraceptives,
ranitidine, ranolazine,
tipranavir/ritonavir, zileuton
Please note that this is not an exhaustive list.
a A strong inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a substrate for that
CYP by equal or more than 5-fold.
b A moderate inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate
for that CYP by less than 5-fold but equal to or more than 2-fold.
c A weak inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate for
that CYP by less than 2-fold but equal to or more than 5-fold.
d The effect of grapefruit juice varies widely among brands and is concentration, dose, and preparation dependent. 
Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used (eg, 
high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (eg, low dose, 
single strength).
e Withdrawn from the United States market because of safety reasons.
f Herbal product.
Abbreviations: AUC = area under the concentration-time curve; CL = clearance; CYP = cytochrome P450
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Table 2:
Classification of In Vivo Inducers of CYP Enzymes
CYP Enzymes
Strong Inducers
≥80% Decrease in AUC
Moderate Inducers
50%-80% Decrease in AUC
Weak Inducers
20%-50% Decrease in AUC
CYP3A
Avasimibe,a carbamazepine,
phenytoin, rifampin, St.
John’s wortb
Bosentan, efavirenz, etravirine,
modafinil, nafcillin
Amprenavir, aprepitant,
armodafinil, echinacea,c
pioglitazone, prednisone,
rufinamide
Please note that this is not an exhaustive list.
a Not a marketed drug.
b The effect of St. John’s wort varies widely and is preparation dependent.
c Herbal product.
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450.
Table 3:
Examples of Sensitive In Vivo CYP Substrates and CYP Substrates
with Narrow Therapeutic Range
CYP Enzymes
Sensitive Substratesa
Substrates with Narrow
Therapeutic Rangeb
CYP3A
Alfentanil, aprepitant, budesonide, buspirone,
conivaptan, darifenacin, darunavir, dasatinib,
dronedarone, eletriptan, eplerenone, everolimus,
felodipine, indinavir, fluticasone, lopinavir,
lovastatin, lurasidone, maraviroc, midazolam,
nisoldipine, quetiapine, saquinavir, sildenafil,
simvastatin, sirolimus, tolvaptan, tipranavir,
triazolam, vardenafil
Alfentanil, astemizole,c cisapride,c
cyclosporine, dihydroergotamine,
ergotamine, fentanyl, pimozide,
quinidine, sirolimus, tacrolimus,
terfenadinec
CYP2B6
Bupropion, efavirenz
Please note that this is not an exhaustive list.
a Sensitive CYP substrates refers to drugs whose plasma AUC values have been shown to increase 5-fold or higher
when co-administered with a known CYP inhibitor.
b CYP substrates with narrow therapeutic range refers to drugs whose exposure-response relationship indicates that
small increases in their exposure levels by the concomitant use of CYP inhibitors may lead to serious safety concerns
(eg, Torsades de Pointes).
c Withdrawn from the United States market because of safety reasons.
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450
Protocol Amendment No.: 02
Date: 17-Sep-2021
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Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
APPENDIX 7
INTERPRETATION OF HEPATITIS B SEROLOGICAL TEST 
RESULTS
As study treatment in this study is expected to demonstrate immunosuppressive effects, it is
imperative to carefully evaluate and exclude participants with potentially active hepatitis B
infection. For this reason, in order to fully evaluate a participant’s eligibility for enrollment, the
exclusion criterion (see Section 6.2) requires interpretation of data from 3 standard tests for
hepatitis B, ie, measurement of hepatitis B surface antigen (HBsAg), hepatitis B core antigen
antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs).
Participant’s eligibility for enrollment should be assessed as described below. Participants that are:

Hepatitis B serological test negative (neg) for all results may be included in the study

HBsAg (neg), anti-HBc (neg), and anti-HBs positive (POS) may be included in the study 
(immunized due to hepatitis B vaccination)

HBsAg (neg), anti-HBc (POS), and anti-HBs (POS) are to be excluded from the study (immune 
due to natural infection exposure)

Participants that are HBsAg (POS) are excluded from the study (acute or chronic infection)

Participants that are anti-HBc (POS) are excluded from the study (acute or chronic infection)

Participants that are HBsAg (neg), anti-HBc (POS), and anti-HBs (neg) are to be excluded
from the study (interpretation unclear)
Please also refer to the following “Interpretation of Hepatitis B Serologic Test Results” provided 
by the Department of Health and Human Services, Centers for Disease Control and Prevention.
Protocol Amendment No.: 02
Date: 17-Sep-2021
83
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930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
84
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
85
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
86
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
87
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
88
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
89
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
90
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
91
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
92
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
Protocol Amendment No.: 02
Date: 17-Sep-2021
93
4.0
Approved
930164095
4.0
v
Approved
1.0
v


Clinical Protocol
CV006037
BMS-986141
PAR4 Antagonist 
APPENDIX 9
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for the Protocol Amendment 01, 18-Mar-2021
The purpose of this amendment is to change the dosage and dose formulation of BMS-986141 and 
add restrictions for enrollment if participants received the SARS-CoV-2 vaccine. BMS-986141 
will be dosed as a tablet and participants will receive 4 mg tablets as their dose.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section Number & 
Title
Description of Change
Brief Rationale
Section 5.1: Overall 
Design
Changed BMS-986141 to a 4 mg 
dose.
Dose was changed to 4 mg.
Section 5.1: Study 
Design Schematic
Changed BMS-986141 to a 4 mg 
dose.
Dose was changed to 4 mg.
Section 5.4: 
Scientific Rationale 
for Study Design
Changed BMS-986141 to a 4 mg 
dose.
Dose was changed to 4 mg.
Section 5.5: 
Justification for 
Dose
Changed BMS-986141 to a 4 mg 
dose.
Dose was changed to 4 mg.
Section 7: 
Treatment
Changed BMS-986141 to a 4 mg 
tablet.
Dose was changed to 4 mg and 
formulation was changed to a tablet.
Table 7.1: Study 
Treatments for 
CV006037
Changed BMS-986141 to a 4 mg 
tablet.
Dose was changed to 4 mg and 
formulation was changed to a tablet.
Section 7.1: 
Treatments 
Administered
Removed wording for the 
inclusion of a rinse.
Only 240 mL of water will be given 
with the tablet dose; rinse is no 
longer necessary.
Table 7.1-1: 
Selection and 
Timing of Dose
Changed BMS-986141 to a 4 mg 
dose.
Dose was changed to 4 mg.
Section 7.7.1: 
Prohibited and/or 
Restricted 
Treatments
Added information and 
restriction for SARS-CoV-2 
vaccine.
Clarified that SARS-CoV-2 vaccine 
requirements for enrollment.
Section 9.3: 
Overdose
Changed BMS-986141 to a 4 mg 
dose.
Dose was changed to 4 mg.
All
Minor formatting and 
typographical corrections 
throughout.
These have been corrected but not 
summarized here.
Protocol Amendment No.: 02
Date: 17-Sep-2021
94
4.0
Approved
930164095
4.0
v
Approved
1.0
v