A Study on BMS-986177 for the Prevention of a Stroke in Patients Receiving Aspirin and Clopidogrel (AXIOMATIC-SSP)

• ClinicalTrials.gov Identifier: NCT03766581
• Recruitment Status: Completed
• First Posted: December 6, 2018
• Results First Posted: June 12, 2023
• Last Update Posted: June 12, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Janssen, LP
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Acute Ischemic Stroke; Transient Ischemic Attack (TIA)
• Interventions: Drug: BMS-986177; Other: Placebo; Drug: Clopidogrel; Drug: Aspirin
• Enrollment: 2366

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Period Title: Randomization
Started	691	328	318	328	310	351	22	18
Completed	682	324	313	325	306	345	22	17
Not Completed	9	4	5	3	4	6	0	1
Reason Not Completed
Other reasons	2	1	0	1	0	0	0	0
Participant no longer meets study criteria	5	3	4	0	2	3	0	1
Participant request to discontinue study treatment	1	0	0	0	1	2	0	0
Participant withdrew consent	1	0	1	2	1	1	0	0
Period Title: Treatment
Started	682	325 [1]	313	325	306	344 [1]	22	17
Completed	529	260	242	251	230	240	15	14
Not Completed	153	65	71	74	76	104	7	3
Reason Not Completed
Adverse Event	82	44	47	46	50	77	5	2
Participant request to discontinue treatment	34	6	10	10	14	15	0	1
Participant withdrew consent	11	4	5	5	4	4	0	0
Death	1	0	0	0	0	0	0	0
Lost to Follow-up	1	0	0	1	0	0	0	0
Poor/Non compliance	2	2	1	1	1	1	0	0
Participant no longer meets study criteria	9	1	5	4	4	4	2	0
Other reasons	13	8	3	7	3	3	0	0
[1] 1 participant was randomized to Milvexian 200 mg BID, but received Milvexian 25 mg QD.

Baseline Characteristics

Arm/Group Title		Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD	Total
Arm/Group Description		Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Total of all reporting groups
Overall Number of Baseline Participants		691	328	318	328	310	351	22	18	2366
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	691 participants	328 participants	318 participants	328 participants	310 participants	351 participants	22 participants	18 participants	2366 participants
		69.1 (10.58)	70.9 (10.66)	70.1 (11.34)	69.3 (10.69)	69.7 (10.59)	69.5 (11.11)	65.7 (10.64)	65.4 (11.65)	69.6 (10.81)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	691 participants	328 participants	318 participants	328 participants	310 participants	351 participants	22 participants	18 participants	2366 participants
	Female	254 36.8%	109 33.2%	118 37.1%	121 36.9%	112 36.1%	128 36.5%	7 31.8%	10 55.6%	859 36.3%
	Male	437 63.2%	219 66.8%	200 62.9%	207 63.1%	198 63.9%	223 63.5%	15 68.2%	8 44.4%	1507 63.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	691 participants	328 participants	318 participants	328 participants	310 participants	351 participants	22 participants	18 participants	2366 participants
	Hispanic or Latino	10 1.4%	4 1.2%	2 0.6%	1 0.3%	2 0.6%	1 0.3%	1 4.5%	1 5.6%	22 0.9%
	Not Hispanic or Latino	62 9.0%	20 6.1%	22 6.9%	23 7.0%	29 9.4%	27 7.7%	7 31.8%	7 38.9%	197 8.3%
	Unknown or Not Reported	619 89.6%	304 92.7%	294 92.5%	304 92.7%	279 90.0%	323 92.0%	14 63.6%	10 55.6%	2147 90.7%
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	691 participants	328 participants	318 participants	328 participants	310 participants	351 participants	22 participants	18 participants	2366 participants
White		549 79.5%	257 78.4%	246 77.4%	260 79.3%	251 81.0%	288 82.1%	18 81.8%	15 83.3%	1884 79.6%
Black or African American		15 2.2%	5 1.5%	6 1.9%	8 2.4%	3 1.0%	5 1.4%	3 13.6%	3 16.7%	48 2.0%
Asian		35 5.1%	12 3.7%	21 6.6%	13 4.0%	11 3.5%	17 4.8%	0 0.0%	0 0.0%	109 4.6%
Native Hawaiian or Other Pacific Islander		0 0.0%	1 0.3%	1 0.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 0.1%
Asian Indian		2 0.3%	1 0.3%	2 0.6%	1 0.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	6 0.3%
Chinese		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.3%	0 0.0%	0 0.0%	0 0.0%	1 0.0%
Japanese		84 12.2%	46 14.0%	40 12.6%	41 12.5%	39 12.6%	40 11.4%	0 0.0%	0 0.0%	290 12.3%
Malay		1 0.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.0%
Asian Other		0 0.0%	0 0.0%	0 0.0%	1 0.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.0%
Other		5 0.7%	6 1.8%	2 0.6%	4 1.2%	5 1.6%	1 0.3%	1 4.5%	0 0.0%	24 1.0%
		[1] Measure Description: Race

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With Model Based Assessment of Composite of New Ischemic Stroke During Treatment and New Covert Brain Infarction (FLAIR + DWI) Detected by MRI by Day 90
Description	Model based assessment estimate for composite event is a customized statistical analysis called MCP-MOD (Multiple Comparison Procedures, MODel) estimation, which is used to check for dose-response relationship. 95% confidence interval (CI) for composite event based on bootstrap (10000 samples).
Time Frame	From randomization to up to 90 days after randomization

Outcome Measure Data

Analysis Population Description

All randomized participants who experienced a new ischemic stroke by day 90, or an evaluable day 90 MRI regardless of when the MRI was collected. Dose -response model-based endpoint that was pre-specified for data to be collected only in the Placebo, 25 mg QD, and BID dose regimens.

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	625	308	287	306	277	317
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	16.8; (14.2 to 19.4)	16.7; (14.4 to 19.0)	16.6; (14.5 to 18.7)	15.6; (13.6 to 17.9)	15.4; (13.0 to 18.0)	15.3; (12.3 to 20.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 25 mg QD
	Comments	Milvexian 25 mg QD over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	MCP-MOD
	Comments	Multiple Comparison Procedures, MODel
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.10
	Estimation Comments	95% confidence interval (CI) for composite event based on bootstrap (10000 samples)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 25 mg BID
	Comments	Milvexian 25 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	MCP-MOD
	Comments	Multiple Comparison Procedures, MODel
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.15
	Estimation Comments	95% confidence interval (CI) for composite event based on bootstrap (10000 samples)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 50 mg BID
	Comments	Milvexian 50 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	MCP-MOD
	Comments	Multiple Comparison Procedures, MODel
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.16
	Estimation Comments	95% confidence interval (CI) for composite event based on bootstrap (10000 samples)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 100 mg BID
	Comments	Milvexian 100 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	MCP-MOD
	Comments	Multiple Comparison Procedures, MODel
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.18
	Estimation Comments	95% confidence interval (CI) for composite event based on bootstrap (10000 samples)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 200 mg BID
	Comments	Milvexian 200 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	MCP-MOD
	Comments	Multiple Comparison Procedures, MODel
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.31
	Estimation Comments	95% confidence interval (CI) for composite event based on bootstrap (10000 samples)

2. Secondary Outcome

Title	Percent of Participants With Major Bleeding According to BARC Type 3 and 5
Description	Percent of participants with major bleeding based on the Bleeding Academic Research Consortium (BARC) Types 3 and 5 definitions. BARC bleeding types: 3a = Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL transfusion with overt bleeding 3b = Overt bleeding plus hemoglobin drop ≥5 g/dL; cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents 3c = Intracranial hemorrhage, 5a = Probable fatal bleeding 5b = Definite fatal bleeding
Time Frame	From first dose to up to 107 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	0.6; (0.2 to 1.5)	0.6; (0.1 to 2.2)	0.6; (0.1 to 2.3)	1.5; (0.5 to 3.6)	1.6; (0.5 to 3.8)	1.5; (0.5 to 3.4)	0; (0 to 15.4)	0; (0 to 19.5)

3. Secondary Outcome

Title	Number of Participants With Bleeding Based on BARC Types 1-5
Description	Number of participants with bleeding based on Bleeding Academic Research Consortium (BARC) Type 1 to 5. BARC bleeding types: 0=No bleeding. 1=Not actionable bleeding. 2=Overt, actionable sign of hemorrhage requiring nonsurgical, medical intervention by a health-care professional, leading to hospitalization or increased level of care, or prompting evaluation. 3a=Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL. 3b=Overt bleeding plus hemoglobin drop ≥5 g/dL; cardiac tamponade; bleeding requiring surgical intervention; bleeding requiring IV vasoactive agents. 3c=Intracranial hemorrhage; intraocular bleed compromising vision. 4=CABG-related bleeding, perioperative intracranial bleeding within 48 hours, reoperation after closure of sternotomy to control bleeding, transfusion of ≥5 U whole blood or packed red blood cells within a 48-hour period, chest tube output more than or equal to 2L within a 24-hour period. 5a=Probable fatal bleeding. 5b=Definite fatal bleeding.
Time Frame	From first dose to up to 107 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
Type 1	41 6.0%	26 8.0%	16 5.1%	28 8.6%	25 8.2%	22 6.4%	5 22.7%	2 11.8%
Type 2	9 1.3%	7 2.2%	9 2.9%	7 2.2%	10 3.3%	8 2.3%	1 4.5%	1 5.9%
Type 3A	2 0.3%	1 0.3%	1 0.3%	1 0.3%	2 0.7%	3 0.9%	0 0.0%	0 0.0%
Type 3B	0 0.0%	1 0.3%	1 0.3%	1 0.3%	3 1.0%	1 0.3%	0 0.0%	0 0.0%
Type 3C	2 0.3%	0 0.0%	0 0.0%	3 0.9%	0 0.0%	1 0.3%	0 0.0%	0 0.0%
Type 4	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Type 5A	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Type 5B	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

4. Secondary Outcome

Title	Number of Participants With Bleeding Based on ISTH-Defined Criteria
Description	Number of participants with bleeding based on International Society on Thrombosis and Hemostasis (ISTH). ISTH Bleeding Types: 1) Fatal bleeding and/or 2) Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome and/or 3) Bleeding causing a fall in hemoglobin level of ≥2 g/dL, or leading to transfusion of ≥2 units of whole blood or red cells.
Time Frame	From first dose to up to 107 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
Major	4 0.6%	2 0.6%	2 0.6%	5 1.5%	6 2.0%	5 1.5%	0 0.0%	0 0.0%
Clinically Relevant Non-Major (CRNM)	7 1.0%	8 2.5%	9 2.9%	7 2.2%	8 2.6%	8 2.3%	1 4.5%	1 5.9%
Major or CRNM	11 1.6%	10 3.1%	11 3.5%	12 3.7%	14 4.6%	13 3.8%	1 4.5%	1 5.9%
Minor Bleed	43 6.3%	25 7.7%	16 5.1%	28 8.6%	26 8.5%	22 6.4%	5 22.7%	2 11.8%

5. Secondary Outcome

Title	Number of Participants With Bleeding Based on PLATO-Defined Criteria
Description	Number of participants with bleeding based on Platelet Inhibition and Patient Outcomes (PLATO) defined criteria. PLATO bleeding definitions: Major Life-threatening: Fatal, Intracranial, Intrapericardial with cardiac tamponade, Resulting in hypovolemic shock or severe hypotension that requires pressors or surgery, Clinically overt or apparent bleeding associated with decrease in hemoglobin >5 g/dL, Requiring transfusion of ≥4 U whole blood or packed red blood cells (PRBCs); Other Major: Significantly disabling (eg, intraocular with permanent vision loss), Associated drop in hemoglobin of 3 to 5 g/dL, Requiring transfusion of 2 to 3 U whole blood or PRBCs; Any Major: Any one of the above criteria; Minor: Bleeding that does not meet criteria for PLATO Major bleeding, and requiring medical intervention
Time Frame	From first dose to up to 107 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
MAJOR LIFE-THREATENING	2 0.3%	1 0.3%	1 0.3%	4 1.2%	3 1.0%	2 0.6%	0 0.0%	0 0.0%
OTHER MAJOR BLEEDING	2 0.3%	1 0.3%	1 0.3%	1 0.3%	2 0.7%	3 0.9%	0 0.0%	0 0.0%
ANY MAJOR	4 0.6%	2 0.6%	2 0.6%	5 1.5%	5 1.6%	5 1.5%	0 0.0%	0 0.0%
MINOR	7 1.0%	6 1.8%	7 2.2%	7 2.2%	9 2.9%	9 2.6%	0 0.0%	1 5.9%
MINIMAL	43 6.3%	27 8.3%	18 5.8%	28 8.6%	26 8.5%	21 6.1%	6 27.3%	2 11.8%

6. Secondary Outcome

Title	Percent of Participants With Descriptive Assessment of Composite of New Ischemic Stroke During Treatment and New Covert Brain Infarction (FLAIR + DWI) Detected by MRI by Day 90
Description	Descriptive Assessment of Composite of New Ischemic Stroke During Treatment and New Covert Brain Infarction (FLAIR + DWI) Detected by MRI by Day 90.
Time Frame	From randomization to up to 90 days after randomization

Outcome Measure Data

Analysis Population Description

All randomized participants who experienced a new ischemic stroke by day 90, or an evaluable day 90 MRI regardless of when the MRI was collected.

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	625	308	287	306	277	317	21	16
Measure Type: Number; Unit of Measure: Percentage of participants
	16.6	16.2	18.5	14.1	14.8	16.4	19.0	18.8

7. Secondary Outcome

Title	Composite of Percent of Participants With New Ischemic Stroke, MI and All Cause Death
Description	Composite of percent of participants of new ischemic stroke, (Myocardial Infarction) MI and all cause death.
Time Frame	From randomization to up to 90 days after randomization

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	691	328	318	328	310	351	22	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	6.1; (4.3 to 7.9)	5.2; (2.8 to 7.6)	4.7; (2.4 to 7.0)	4.9; (2.5 to 7.2)	5.2; (2.7 to 7.6)	9.4; (6.3 to 12.5)	18.2; (2.1 to 34.3)	5.6; (0 to 16.1)

8. Secondary Outcome

Title	National Institutes of Health Stroke Scale (NIHSS)
Description	The NIHSS is an 11-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. The score for each ability is a number between 0 and 4, 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. In the NIHSS, the higher the score, the more impaired a stroke participant is.
Time Frame	At baseline, on Days 21 and 90, and at the time of a new stroke event

Outcome Measure Data

Analysis Population Description

All randomized participants with a complete NIHSS assessment

Arm/Group Title		Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:		Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed		684	324	311	326	305	348	22	17
Mean (Standard Deviation); Unit of Measure: Score on a scale
Baseline	Number Analyzed	684 participants	324 participants	311 participants	326 participants	305 participants	348 participants	22 participants	17 participants
		1.6 (1.87)	1.7 (1.68)	1.6 (1.73)	1.6 (1.79)	1.8 (1.81)	1.6 (1.79)	1.1 (1.44)	2.0 (1.70)
Day 21	Number Analyzed	624 participants	294 participants	280 participants	301 participants	271 participants	314 participants	18 participants	16 participants
		0.9 (2.11)	0.8 (1.35)	0.8 (1.43)	0.8 (1.58)	0.8 (1.48)	0.9 (1.88)	0.8 (1.90)	0.9 (1.39)
Day 90	Number Analyzed	552 participants	263 participants	251 participants	259 participants	238 participants	256 participants	20 participants	14 participants
		0.5 (1.40)	0.6 (1.06)	0.6 (1.51)	0.6 (1.14)	0.6 (1.32)	0.6 (1.29)	0.3 (0.72)	0.6 (1.45)
First recurrent stroke	Number Analyzed	29 participants	14 participants	11 participants	11 participants	10 participants	20 participants	3 participants	1 participants
		6.2 (5.01)	4.6 (6.79)	5.4 (3.17)	4.6 (4.30)	7.1 (4.68)	4.4 (4.60)	5.3 (3.06)	1.0 [1] (NA)

[1]

Insufficient number of participants with events

9. Secondary Outcome

Title	Modified Rankin Scale (mRS)
Description	The Modified Rankin Score (mRS) is a 6-point disability scale with possible scores ranging from 0 to 6. 0 = No symptoms at all; = No significant disability despite symptoms; able to carry out all usual duties and activities; = Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; = Moderate disability; requiring some help, but able to walk without assistance; = Moderately severe disability; unable to walk and attend to bodily needs without assistance; = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; = Dead
Time Frame	At baseline, on Days 21 and 90, and at the time of a new stroke event

Outcome Measure Data

Analysis Population Description

All randomized participants with a complete mRS assessment

Arm/Group Title		Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:		Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed		688	326	314	328	309	349	22	17
Mean (Standard Deviation); Unit of Measure: Score on a scale
Baseline	Number Analyzed	688 participants	326 participants	314 participants	328 participants	309 participants	349 participants	22 participants	17 participants
		0.5 (0.87)	0.6 (0.95)	0.6 (0.96)	0.5 (0.86)	0.5 (0.89)	0.6 (0.95)	0.2 (0.53)	0.7 (0.99)
Day 21	Number Analyzed	630 participants	301 participants	287 participants	306 participants	279 participants	316 participants	17 participants	16 participants
		1.0 (1.18)	1.0 (1.13)	0.9 (1.15)	0.9 (1.15)	1.0 (1.17)	0.9 (1.19)	0.9 (1.27)	1.3 (1.14)
Day 90	Number Analyzed	562 participants	269 participants	257 participants	265 participants	245 participants	259 participants	20 participants	14 participants
		0.7 (1.04)	0.8 (1.04)	0.8 (1.07)	0.7 (1.01)	0.7 (1.01)	0.8 (1.05)	0.6 (1.05)	1.0 (1.11)
First recurrent stroke	Number Analyzed	26 participants	13 participants	10 participants	11 participants	8 participants	19 participants	2 participants	1 participants
		3.0 (1.60)	2.7 (1.03)	2.6 (1.35)	2.3 (1.62)	2.9 (1.64)	1.8 (1.72)	2.0 (0.00)	1.0 [1] (NA)

[1]

Insufficient number of participants with events

10. Secondary Outcome

Title	Montreal Cognitive Assessment (MoCA)
Description	The Montreal Cognitive Assessment (MoCA) is a survey with a summed score. MoCA score ranges between a lowest score of 0 to a highest score of 30. A score of: ≥26 points: indicates normal cognitive function; 18-25 points: Mild cognitive impairment; 10-17 points: Moderate cognitive impairment; fewer than 10 points: Severe cognitive impairment
Time Frame	At baseline, on Days 21 and 90, and at the time of a new stroke event

Outcome Measure Data

Analysis Population Description

All randomized participants with a complete MoCA assessment

Arm/Group Title		Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:		Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed		541	257	235	257	235	276	17	14
Mean (Standard Deviation); Unit of Measure: Score on a scale
Baseline	Number Analyzed	541 participants	257 participants	235 participants	257 participants	235 participants	276 participants	17 participants	14 participants
		22.3 (5.06)	21.6 (5.59)	22.0 (5.18)	22.5 (4.82)	22.4 (5.04)	22.1 (5.31)	24.4 (3.84)	22.0 (4.59)
Day 21	Number Analyzed	492 participants	231 participants	206 participants	236 participants	211 participants	251 participants	15 participants	13 participants
		24.0 (4.77)	23.9 (5.01)	24.0 (4.70)	24.3 (4.57)	23.6 (4.48)	24.0 (4.96)	26.4 (2.61)	24.1 (4.70)
Day 90	Number Analyzed	435 participants	208 participants	183 participants	209 participants	180 participants	210 participants	15 participants	11 participants
		24.6 (4.54)	24.0 (4.69)	24.2 (4.80)	24.4 (4.48)	24.5 (4.36)	24.2 (5.05)	25.0 (4.72)	26.4 (1.69)
First recurrent stroke	Number Analyzed	10 participants	3 participants	3 participants	2 participants	1 participants	8 participants	1 participants	1 participants
		23.2 (6.63)	17.3 (6.11)	25.3 (2.31)	19.0 (8.49)	3.0 [1] (NA)	23.1 (7.08)	11.0 [1] (NA)	22.0 [1] (NA)

[1]

Insufficient number of participants with events

11. Secondary Outcome

Title	Digit Symbol Substitution Test (DSST)
Description	The Descriptive Summary of the Digit Symbol Substitution Test (DSST) is a scale item, with a lowest score of 0 and highest total score of 135. Higher score indicates better cognitive functioning.
Time Frame	At baseline, on Days 21 and 90, and at the time of a new stroke event

Outcome Measure Data

Analysis Population Description

All randomized participants with a complete DSST assessment

Arm/Group Title		Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:		Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed		493	238	209	234	220	257	17	14
Mean (Standard Deviation); Unit of Measure: Score on a scale
Baseline	Number Analyzed	493 participants	238 participants	209 participants	234 participants	220 participants	257 participants	17 participants	14 participants
		34.9 (22.36)	31.2 (18.87)	32.9 (22.89)	37.2 (25.67)	33.7 (21.89)	31.7 (19.15)	47.1 (29.34)	29.2 (18.16)
Day 21	Number Analyzed	443 participants	213 participants	183 participants	213 participants	194 participants	228 participants	14 participants	13 participants
		41.2 (22.14)	38.9 (19.27)	40.2 (21.60)	45.1 (25.77)	41.2 (22.87)	39.1 (21.35)	54.6 (32.73)	37.1 (20.13)
Day 90	Number Analyzed	394 participants	191 participants	160 participants	186 participants	166 participants	192 participants	15 participants	11 participants
		42.8 (21.18)	41.7 (21.66)	41.3 (20.29)	45.2 (21.86)	45.5 (23.44)	41.4 (21.97)	47.5 (27.48)	40.7 (17.46)
First recurrent stroke	Number Analyzed	8 participants	3 participants	3 participants	2 participants	1 participants	6 participants	1 participants	1 participants
		36.3 (13.56)	28.0 (20.95)	42.0 (4.36)	40.5 (2.12)	23.0 [1] (NA)	27.5 (16.96)	9.0 [1] (NA)	47.0 [1] (NA)

[1]

Insufficient number of participants with events

12. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	AE: include all non-serious adverse events with onset on or after first dose date and within 2 days after the last dose of study treatment.
Time Frame	From first dose to 2 days after last dose of study therapy (up to approximately 107 days)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
	399 58.5%	190 58.5%	186 59.4%	192 59.1%	193 63.1%	211 61.3%	11 50.0%	13 76.5%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Vital Sign Abnormalities
Description	Number of participants with clinically significant vital sign abnormalities. Vital signs included heart rate and diastolic and systolic blood pressure.
Time Frame	From first dose to up to 90 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

14. Secondary Outcome

Title	Number of Participants With Clinically Significant Physical Examination Abnormalities
Description	Number of participants with clinically significant physical examination abnormalities.
Time Frame	From first dose to up to 90 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

15. Secondary Outcome

Title	Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Description	Number of participants with clinically significant ECG abnormalities.
Time Frame	From first dose to up to 90 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	682	325	313	325	306	344	22	17
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

16. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities - Liver
Description	The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Results reported in International System of Units (SI)
Time Frame	From first dose to up to approximately 38 months

Outcome Measure Data

Analysis Population Description

All treated participants with at least one clinically significant liver laboratory abnormality

Arm/Group Title		Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:		Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed		642	303	280	306	281	324	21	16
Measure Type: Count of Participants; Unit of Measure: Participants
ALT > 3x ULN	Number Analyzed	642 participants	303 participants	280 participants	306 participants	280 participants	324 participants	20 participants	16 participants
		4 0.6%	2 0.7%	0 0.0%	2 0.7%	3 1.1%	3 0.9%	0 0.0%	0 0.0%
ALT > 5x ULN	Number Analyzed	642 participants	303 participants	280 participants	306 participants	280 participants	324 participants	20 participants	16 participants
		1 0.2%	0 0.0%	0 0.0%	0 0.0%	2 0.7%	2 0.6%	0 0.0%	0 0.0%
ALT > 10x ULN	Number Analyzed	642 participants	303 participants	280 participants	306 participants	280 participants	324 participants	20 participants	16 participants
		1 0.2%	0 0.0%	0 0.0%	0 0.0%	1 0.4%	1 0.3%	0 0.0%	0 0.0%
ALT > 20x ULN	Number Analyzed	642 participants	303 participants	280 participants	306 participants	280 participants	324 participants	20 participants	16 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.4%	0 0.0%	0 0.0%	0 0.0%
AST > 3x ULN	Number Analyzed	641 participants	302 participants	280 participants	304 participants	281 participants	323 participants	21 participants	16 participants
		6 0.9%	5 1.7%	1 0.4%	4 1.3%	3 1.1%	3 0.9%	1 4.8%	0 0.0%
AST > 5x ULN	Number Analyzed	641 participants	302 participants	280 participants	304 participants	281 participants	323 participants	21 participants	16 participants
		3 0.5%	2 0.7%	1 0.4%	0 0.0%	2 0.7%	1 0.3%	1 4.8%	0 0.0%
AST > 10x ULN	Number Analyzed	641 participants	302 participants	280 participants	304 participants	281 participants	323 participants	21 participants	16 participants
		1 0.2%	0 0.0%	0 0.0%	0 0.0%	1 0.4%	0 0.0%	0 0.0%	0 0.0%
AST > 20x ULN	Number Analyzed	641 participants	302 participants	280 participants	304 participants	281 participants	323 participants	21 participants	16 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.4%	0 0.0%	0 0.0%	0 0.0%
ALP > 2x ULN	Number Analyzed	640 participants	300 participants	276 participants	305 participants	279 participants	319 participants	20 participants	16 participants
		4 0.6%	5 1.7%	1 0.4%	6 2.0%	4 1.4%	2 0.6%	0 0.0%	0 0.0%
Total Bilirubin > 1.5x ULN	Number Analyzed	639 participants	302 participants	277 participants	304 participants	279 participants	318 participants	20 participants	16 participants
		10 1.6%	6 2.0%	2 0.7%	7 2.3%	5 1.8%	2 0.6%	0 0.0%	0 0.0%
Total Bilirubin > 2x ULN	Number Analyzed	639 participants	302 participants	277 participants	304 participants	279 participants	318 participants	20 participants	16 participants
		3 0.5%	1 0.3%	1 0.4%	2 0.7%	2 0.7%	1 0.3%	0 0.0%	0 0.0%
Concurrent ALT/AST Elevation > 3x ULN with total bilirubin >2x ULN	Number Analyzed	639 participants	302 participants	277 participants	304 participants	279 participants	318 participants	20 participants	16 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.4%	0 0.0%	0 0.0%	0 0.0%

17. Secondary Outcome

Title	Percent Change From Baseline in aPTT Activity
Description	Percent change from baseline in activated partial thromboplastin time (aPTT) activity via exposure response.
Time Frame	Baseline and day 90

Outcome Measure Data

Analysis Population Description

All participants with at least one aPTT pharmacodynamic endpoint assessed after first dose

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	503	251	226	241	214	232	14	14
Mean (Standard Error); Unit of Measure: Percent change
	2.47 (0.768)	38.72 (2.264)	58.30 (3.195)	97.32 (3.601)	140.76 (5.154)	193.64 (7.041)	48.48 (11.243)	118.06 (13.840)

18. Secondary Outcome

Title	Percent Change From Baseline in Factor XI Clotting Activity
Description	Percent change from baseline in factor XI clotting activity via exposure response.
Time Frame	Baseline and day 90

Outcome Measure Data

Analysis Population Description

All participants with at least one factor XI clotting pharmacodynamic endpoint assessed after first dose

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	503	251	223	228	216	236	15	13
Mean (Standard Error); Unit of Measure: Percent change
	4.48 (3.455)	-8.88 (1.280)	-17.67 (1.900)	-37.20 (1.655)	-61.52 (1.869)	-70.25 (3.043)	3.86 (13.754)	-44.27 (6.501)

19. Secondary Outcome

Title	Pharmacokinetic Parameter - Estimated Clearance (CL)
Description	Pharmacokinetic Parameter - Estimated Clearance (CL). CL is derived from plasma concentration versus time data. PK parameters were generated using a Population Pharmacokinetics (PPK) model. Summary statistics for these individual predicted PK parameters and exposures were stratified by dose. The PPK model analysis was based on combined PK data collected on days 1, 21, and 90.
Time Frame	From first dose to up to 90 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants with at least one post-dose PK sample. Pre-specified for data to be collected only in the 25 mg QD, and BID dose regimens.

Arm/Group Title	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	323	307	323	303	341
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: L/h
	8.15; (34%)	8.01; (34.3%)	7.54; (32.8%)	7.08; (31.3%)	7.43; (32.9%)

20. Secondary Outcome

Title	Pharmacokinetic Parameter - Volume of the Central Compartment (VC)
Description	Pharmacokinetic Parameter - Volume of the Central Compartment (VC). VC is derived from plasma concentration versus time data. PK parameters were generated using a Population Pharmacokinetics (PPK) model. Summary statistics for these individual predicted PK parameters and exposures were stratified by dose. The PPK model analysis was based on combined PK data collected on days 1, 21, and 90.
Time Frame	From first dose to up to 90 days after first dose

Outcome Measure Data

Analysis Population Description

All treated participants with at least one post-dose PK sample. Pre-specified for data to be collected only in the 25 mg QD, and BID dose regimens.

Arm/Group Title	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	323	307	323	303	341
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: L
	34.9; (152%)	31.4; (138%)	30.9; (145%)	28.9; (149%)	31.6; (181%)

21. Secondary Outcome

Title	Volume of Incident Infarcts (New DWI+ or DWI- Lesions) by Participant on Day 90 MRI
Description	Total volume of diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) infarcts on the DWI Sequence on day 90 MRI.
Time Frame	At day 90

Outcome Measure Data

Analysis Population Description

All randomized participants with an evaluable MRI

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	82	40	49	36	35	35	3	3
Mean (Standard Deviation); Unit of Measure: mL
	2.3492 (11.40906)	0.8976 (1.96342)	2.9902 (8.28993)	1.2682 (2.72452)	1.4727 (3.78795)	1.2711 (4.05035)	8.8960 (13.85294)	1.4503 (1.89112)

22. Secondary Outcome

Title	Number of Incident Infarcts (New DWI+ or DWI- Lesions) by Participant on Day 90 MRI
Description	Number of diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) infarcts on the DWI Sequence on day 90 MRI.
Time Frame	At day 90

Outcome Measure Data

Analysis Population Description

All randomized participants with an evaluable MRI

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	82	40	49	36	35	35	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
>0	82 100.0%	40 100.0%	49 100.0%	36 100.0%	35 100.0%	35 100.0%	3 100.0%	3 100.0%
1	57 69.5%	26 65.0%	36 73.5%	26 72.2%	24 68.6%	23 65.7%	1 33.3%	2 66.7%
2	11 13.4%	8 20.0%	5 10.2%	5 13.9%	3 8.6%	6 17.1%	2 66.7%	0 0.0%
3	8 9.8%	5 12.5%	4 8.2%	1 2.8%	2 5.7%	2 5.7%	0 0.0%	0 0.0%
4	1 1.2%	1 2.5%	2 4.1%	3 8.3%	2 5.7%	2 5.7%	0 0.0%	1 33.3%
5	1 1.2%	0 0.0%	0 0.0%	0 0.0%	1 2.9%	2 5.7%	0 0.0%	0 0.0%
>5	4 4.9%	0 0.0%	2 4.1%	1 2.8%	3 8.6%	0 0.0%	0 0.0%	0 0.0%

23. Other Pre-specified Outcome

Title	Percent of Participants With Ischemic Stroke Events
Description	Secondary analysis of symptomatic ischemic stroke events. Clinical events are included up to day 90. Wald 95% CI within group. Undetermined stroke is included.
Time Frame	From randomization to up to 90 days after randomization

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID	Milvexian 50 mg QD	Milvexian 100 mg QD
Arm/Group Description:	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.
Overall Number of Participants Analyzed	691	328	318	328	310	351	22	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Ischemic stroke	5.5; (3.8 to 7.2)	4.6; (2.3 to 6.8)	3.8; (1.7 to 5.9)	4.0; (1.9 to 6.1)	3.5; (1.5 to 5.6)	7.7; (4.9 to 10.5)	13.6; (0.0 to 28.0)	5.6; (0.0 to 16.1)
Undetermined stroke	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)	0; (0 to 0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 25 mg QD
	Comments	Milvexian 25 mg QD over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.49
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 25 mg BID
	Comments	Milvexian 25 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.36 to 1.30
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 50 mg BID
	Comments	Milvexian 50 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.33
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 100 mg BID
	Comments	Milvexian 100 mg BID over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.33 to 1.25
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 200 mg BID
	Comments	Milvexian 200 mg BID
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 0.87 to 2.25
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 50 mg QD
	Comments	Milvexian 50 mg QD over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 0.83 to 7.42
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milvexian 100 mg QD
	Comments	Milvexian 100 mg QD over Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Wald Confidence Limits
	Comments	95% CIs for RR are constructed using Wald Confidence Limits
Method of Estimation	Estimation Parameter	Relative Risk (RR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.15 to 6.96
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Participants were assessed for all-cause mortality from their randomization until their study completion (up to approximately 38 months). SAEs and Other AEs were assessed from first dose to 7 days after last dose of study therapy (up to approximately 112 days).
Adverse Event Reporting Description	The total number at risk for all-cause mortality represents all participants who were randomized. The total number at risk by any serious adverse event and other (not including serious) adverse events represents all participants who received at least 1 dose of study medication.
Arm/Group Title	Placebo	Milvexian 25 mg QD	Milvexian 50 mg QD	Milvexian 100 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
Arm/Group Description	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Placebo + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Placebo + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg QD + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg QD + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 25 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 25 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 50 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 50 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 100 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 100 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.	Loading dose of Clopidogrel 300 mg + Aspirin 100 mg followed by Milvexian 200 mg BID + Aspirin 100 mg QD + Clopidogrel 75 mg QD on days 1-21 and Milvexian 200 mg BID + Aspirin 100 mg QD on days 22-90. All administered orally.
All-Cause Mortality
	Placebo	Milvexian 25 mg QD	Milvexian 50 mg QD	Milvexian 100 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/691 (0.72%)	4/328 (1.22%)	0/22 (0.00%)	0/18 (0.00%)	3/318 (0.94%)	3/328 (0.91%)	5/310 (1.61%)	5/351 (1.42%)
Serious Adverse Events
	Placebo	Milvexian 25 mg QD	Milvexian 50 mg QD	Milvexian 100 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	94/682 (13.78%)	37/325 (11.38%)	5/22 (22.73%)	3/17 (17.65%)	39/313 (12.46%)	41/325 (12.62%)	42/306 (13.73%)	54/344 (15.70%)
Blood and lymphatic system disorders
Anaemia † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Cardiac disorders
Acute myocardial infarction † 1	2/682 (0.29%)	0/325 (0.00%)	1/22 (4.55%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Angina pectoris † 1	1/682 (0.15%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Angina unstable † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Atrial fibrillation † 1	4/682 (0.59%)	3/325 (0.92%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	3/306 (0.98%)	0/344 (0.00%)
Atrial flutter † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Atrial tachycardia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Atrioventricular block complete † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	1/306 (0.33%)	0/344 (0.00%)
Atrioventricular block second degree † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Bradycardia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	1/306 (0.33%)	0/344 (0.00%)
Cardiac arrest † 1	2/682 (0.29%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Cardiac failure † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	2/313 (0.64%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Cardiac failure acute † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Cardiac failure congestive † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Cardiac ventricular thrombosis † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Coronary artery disease † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Intracardiac thrombus † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Ischaemic cardiomyopathy † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Myocardial infarction † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	2/306 (0.65%)	1/344 (0.29%)
Myocardial ischaemia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Nodal rhythm † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Pericarditis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Prinzmetal angina † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Sinus tachycardia † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Congenital, familial and genetic disorders
Atrial septal defect † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	2/313 (0.64%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Vertigo positional † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Eye disorders
Retinal detachment † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Duodenal ulcer † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Duodenal ulcer haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Duodenal ulcer perforation † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Faecaloma † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Gastric ulcer haemorrhage † 1	1/682 (0.15%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	2/344 (0.58%)
Gastrointestinal haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Haemorrhoidal haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Mallory-Weiss syndrome † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Nausea † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Oesophagitis haemorrhagic † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Pancreatitis acute † 1	2/682 (0.29%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Peptic ulcer haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Rectal haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Small intestinal haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
General disorders
Asthenia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Pyrexia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Sudden cardiac death † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	2/682 (0.29%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Cholecystitis acute † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Cholelithiasis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Hepatitis fulminant † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Infections and infestations
Arthritis bacterial † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Bronchitis † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
COVID-19 † 1	5/682 (0.73%)	2/325 (0.62%)	0/22 (0.00%)	0/17 (0.00%)	2/313 (0.64%)	1/325 (0.31%)	0/306 (0.00%)	2/344 (0.58%)
Cellulitis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Clostridium difficile infection † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Cystitis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Diverticulitis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Diverticulitis intestinal perforated † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Febrile infection † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Gastroenteritis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Infected dermal cyst † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Large intestine infection † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Osteomyelitis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Pneumonia † 1	3/682 (0.44%)	0/325 (0.00%)	1/22 (4.55%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	2/306 (0.65%)	1/344 (0.29%)
Pneumonia aspiration † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	1/344 (0.29%)
Sepsis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Septic shock † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Staphylococcal bacteraemia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Tuberculosis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Urinary tract infection † 1	1/682 (0.15%)	2/325 (0.62%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	5/344 (1.45%)
Urosepsis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Wound infection pseudomonas † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Injury, poisoning and procedural complications
Accidental overdose † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Cystitis radiation † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Femur fracture † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Fibula fracture † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Forearm fracture † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Post procedural haemorrhage † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Post procedural stroke † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Procedural haemorrhage † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Radius fracture † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Reactive gastropathy † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Skin laceration † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Subdural haematoma † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Investigations
Activated partial thromboplastin time prolonged † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Ejection fraction decreased † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Liver function test increased † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Hyperglycaemia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Hyperkalaemia † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	1/344 (0.29%)
Hypoglycaemia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Hyponatraemia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Type 2 diabetes mellitus † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Osteoarthritis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Breast cancer † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Colon cancer † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Intestinal adenocarcinoma † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Invasive ductal breast carcinoma † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Lung neoplasm malignant † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Metastases to lung † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Metastatic neoplasm † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Sinonasal papilloma † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Squamous cell carcinoma of lung † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Nervous system disorders
Aphasia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Basilar artery occlusion † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Basilar artery stenosis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Basilar migraine † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Brain stem stroke † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Carotid artery stenosis † 1	4/682 (0.59%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Carotid artery thrombosis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Cerebral infarction † 1	4/682 (0.59%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	1/306 (0.33%)	2/344 (0.58%)
Cerebral ischaemia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Cerebral venous thrombosis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Dementia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Dysarthria † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Embolic cerebral infarction † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Encephalopathy † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Epilepsy † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Focal dyscognitive seizures † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Generalised tonic-clonic seizure † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Haemorrhagic transformation stroke † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	2/325 (0.62%)	0/306 (0.00%)	1/344 (0.29%)
Intracranial aneurysm † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Ischaemic cerebral infarction † 1	3/682 (0.44%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	3/313 (0.96%)	2/325 (0.62%)	1/306 (0.33%)	3/344 (0.87%)
Ischaemic stroke † 1	21/682 (3.08%)	9/325 (2.77%)	3/22 (13.64%)	1/17 (5.88%)	6/313 (1.92%)	10/325 (3.08%)	7/306 (2.29%)	11/344 (3.20%)
Lacunar stroke † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Mental impairment † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Myasthenia gravis crisis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Myelopathy † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Neurological symptom † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Partial seizures † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Peroneal nerve palsy † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Pseudostroke † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Sedation complication † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Seizure † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Stroke in evolution † 1	5/682 (0.73%)	2/325 (0.62%)	0/22 (0.00%)	1/17 (5.88%)	4/313 (1.28%)	1/325 (0.31%)	1/306 (0.33%)	8/344 (2.33%)
Syncope † 1	2/682 (0.29%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	1/306 (0.33%)	1/344 (0.29%)
Toxic encephalopathy † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Transient ischaemic attack † 1	8/682 (1.17%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	4/313 (1.28%)	1/325 (0.31%)	4/306 (1.31%)	4/344 (1.16%)
Vertebral artery dissection † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Psychiatric disorders
Anxiety disorder † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Mania † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	3/682 (0.44%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	4/344 (1.16%)
Cystitis haemorrhagic † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Haematuria † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Nephropathy toxic † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	2/344 (0.58%)
Prerenal failure † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Renal failure † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	2/344 (0.58%)
Renal tubular necrosis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Dyspnoea † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Pleural effusion † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Pulmonary embolism † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	1/344 (0.29%)
Pulmonary oedema † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Respiratory failure † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Skin and subcutaneous tissue disorders
Diabetic foot † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	2/313 (0.64%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Drug eruption † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Rash macular † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Toxic epidermal necrolysis † 1	0/682 (0.00%)	0/325 (0.00%)	1/22 (4.55%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Urticaria † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Hypertension † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	1/313 (0.32%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Malignant hypertension † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Orthostatic hypotension † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Peripheral arterial occlusive disease † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Peripheral artery thrombosis † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	0/17 (0.00%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
1 Term from vocabulary, MedDRA 25.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Milvexian 25 mg QD	Milvexian 50 mg QD	Milvexian 100 mg QD	Milvexian 25 mg BID	Milvexian 50 mg BID	Milvexian 100 mg BID	Milvexian 200 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	178/682 (26.10%)	81/325 (24.92%)	6/22 (27.27%)	11/17 (64.71%)	83/313 (26.52%)	92/325 (28.31%)	82/306 (26.80%)	90/344 (26.16%)
Blood and lymphatic system disorders
Anaemia † 1	4/682 (0.59%)	1/325 (0.31%)	0/22 (0.00%)	2/17 (11.76%)	2/313 (0.64%)	2/325 (0.62%)	5/306 (1.63%)	8/344 (2.33%)
Increased tendency to bruise † 1	2/682 (0.29%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Iron deficiency anaemia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Leukocytosis † 1	1/682 (0.15%)	1/325 (0.31%)	0/22 (0.00%)	1/17 (5.88%)	2/313 (0.64%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	5/682 (0.73%)	3/325 (0.92%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	1/325 (0.31%)	2/306 (0.65%)	1/344 (0.29%)
Constipation † 1	44/682 (6.45%)	22/325 (6.77%)	0/22 (0.00%)	3/17 (17.65%)	17/313 (5.43%)	20/325 (6.15%)	20/306 (6.54%)	24/344 (6.98%)
Flatulence † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	2/325 (0.62%)	0/306 (0.00%)	0/344 (0.00%)
Gingival bleeding † 1	3/682 (0.44%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	1/325 (0.31%)	1/306 (0.33%)	1/344 (0.29%)
Nausea † 1	14/682 (2.05%)	11/325 (3.38%)	1/22 (4.55%)	2/17 (11.76%)	6/313 (1.92%)	6/325 (1.85%)	11/306 (3.59%)	5/344 (1.45%)
Rectal haemorrhage † 1	1/682 (0.15%)	0/325 (0.00%)	2/22 (9.09%)	1/17 (5.88%)	0/313 (0.00%)	1/325 (0.31%)	1/306 (0.33%)	2/344 (0.58%)
Vomiting † 1	7/682 (1.03%)	7/325 (2.15%)	0/22 (0.00%)	1/17 (5.88%)	2/313 (0.64%)	3/325 (0.92%)	3/306 (0.98%)	3/344 (0.87%)
General disorders
Fatigue † 1	6/682 (0.88%)	2/325 (0.62%)	0/22 (0.00%)	2/17 (11.76%)	3/313 (0.96%)	1/325 (0.31%)	2/306 (0.65%)	4/344 (1.16%)
Feeling cold † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Non-cardiac chest pain † 1	1/682 (0.15%)	1/325 (0.31%)	0/22 (0.00%)	1/17 (5.88%)	1/313 (0.32%)	2/325 (0.62%)	1/306 (0.33%)	0/344 (0.00%)
Thirst † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	1/344 (0.29%)
Infections and infestations
Urinary tract infection † 1	17/682 (2.49%)	8/325 (2.46%)	0/22 (0.00%)	1/17 (5.88%)	9/313 (2.88%)	6/325 (1.85%)	11/306 (3.59%)	12/344 (3.49%)
Injury, poisoning and procedural complications
Road traffic accident † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Skin abrasion † 1	1/682 (0.15%)	2/325 (0.62%)	0/22 (0.00%)	1/17 (5.88%)	3/313 (0.96%)	1/325 (0.31%)	1/306 (0.33%)	1/344 (0.29%)
Investigations
Activated partial thromboplastin time prolonged † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Metabolism and nutrition disorders
Hyperkalaemia † 1	2/682 (0.29%)	2/325 (0.62%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	2/325 (0.62%)	3/306 (0.98%)	3/344 (0.87%)
Hypocalcaemia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	1/325 (0.31%)	0/306 (0.00%)	0/344 (0.00%)
Hypomagnesaemia † 1	1/682 (0.15%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	2/344 (0.58%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Nervous system disorders
Dizziness † 1	7/682 (1.03%)	4/325 (1.23%)	0/22 (0.00%)	1/17 (5.88%)	4/313 (1.28%)	7/325 (2.15%)	5/306 (1.63%)	2/344 (0.58%)
Headache † 1	23/682 (3.37%)	16/325 (4.92%)	3/22 (13.64%)	1/17 (5.88%)	12/313 (3.83%)	14/325 (4.31%)	12/306 (3.92%)	9/344 (2.62%)
Paraesthesia † 1	3/682 (0.44%)	0/325 (0.00%)	1/22 (4.55%)	2/17 (11.76%)	0/313 (0.00%)	0/325 (0.00%)	1/306 (0.33%)	1/344 (0.29%)
Syncope † 1	1/682 (0.15%)	1/325 (0.31%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	3/325 (0.92%)	0/306 (0.00%)	0/344 (0.00%)
Tremor † 1	3/682 (0.44%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	1/313 (0.32%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Psychiatric disorders
Anxiety † 1	5/682 (0.73%)	3/325 (0.92%)	1/22 (4.55%)	1/17 (5.88%)	6/313 (1.92%)	3/325 (0.92%)	5/306 (1.63%)	3/344 (0.87%)
Depressed mood † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	2/313 (0.64%)	1/325 (0.31%)	0/306 (0.00%)	1/344 (0.29%)
Disorientation † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	1/313 (0.32%)	0/325 (0.00%)	1/306 (0.33%)	0/344 (0.00%)
Mental status changes † 1	0/682 (0.00%)	0/325 (0.00%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	2/682 (0.29%)	0/325 (0.00%)	0/22 (0.00%)	2/17 (11.76%)	1/313 (0.32%)	1/325 (0.31%)	1/306 (0.33%)	9/344 (2.62%)
Pollakiuria † 1	2/682 (0.29%)	1/325 (0.31%)	0/22 (0.00%)	1/17 (5.88%)	0/313 (0.00%)	1/325 (0.31%)	2/306 (0.65%)	1/344 (0.29%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	10/682 (1.47%)	2/325 (0.62%)	2/22 (9.09%)	0/17 (0.00%)	4/313 (1.28%)	5/325 (1.54%)	4/306 (1.31%)	6/344 (1.74%)
Oropharyngeal pain † 1	0/682 (0.00%)	1/325 (0.31%)	0/22 (0.00%)	1/17 (5.88%)	2/313 (0.64%)	0/325 (0.00%)	0/306 (0.00%)	0/344 (0.00%)
Vascular disorders
Hypertension † 1	56/682 (8.21%)	21/325 (6.46%)	0/22 (0.00%)	2/17 (11.76%)	23/313 (7.35%)	24/325 (7.38%)	20/306 (6.54%)	19/344 (5.52%)
Hypotension † 1	5/682 (0.73%)	2/325 (0.62%)	0/22 (0.00%)	1/17 (5.88%)	2/313 (0.64%)	4/325 (1.23%)	1/306 (0.33%)	3/344 (0.87%)
1 Term from vocabulary, MedDRA 25.0; † Indicates events were collected by systematic assessment

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Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please email
• EMail: Clinical.Trials@bms.com

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03766581
• Other Study ID Numbers: CV010-031
• First Submitted: November 13, 2018
• First Posted: December 6, 2018
• Results First Submitted: March 31, 2023
• Results First Posted: June 12, 2023
• Last Update Posted: June 12, 2023