STANDUP AHF: Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03016325
• Collaborator: (none)
• Enrollment: 329
• Locations: 116
• Arms: 5
• Actual Duration (Months): 33.9
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A Study to Evaluate Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of HNO Donor in Hospitalized Patients with Heart Failure and Impaired Systolic Function

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: HNO Donor; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 329 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose-Ranging, Phase 2b Study of the Safety and Efficacy of Continuous 48-Hour Intravenous Infusions of BMS-986231 in Hospitalized Patients With Heart Failure and Impaired Systolic Function
• Actual Study Start Date: Jan 13, 2017
• Actual Primary Completion Date: Jun 23, 2019
• Actual Study Completion Date: Nov 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Cohort 1 HNO Donor	Drug: HNO Donor; Infusion; Other Names: BMS-986231
Placebo Comparator: Placebo Part 1 Cohort 1	Drug: Placebo; Infusion
Experimental: Part 2 Cohort 2 HNO Donor- low dose	Drug: HNO Donor; Infusion; Other Names: BMS-986231
Experimental: Part 2 Cohort 2 HNO Donor- high dose	Drug: HNO Donor; Infusion; Other Names: BMS-986231
Placebo Comparator: Placebo Part 2 Cohort 2	Drug: Placebo; Infusion

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion [From start of infusion up to 6 hours post end of infusion]

   Percentage of participants with clinically relevant hypotension, defined by systolic blood pressure (SBP) < 90 mm Hg (confirmed by a repeated value < 90 mm Hg) or symptoms of hypotension, up to 6 hours after the end of study drug infusion

Secondary Outcome Measures

1. Change in NT-proBNP From Baseline to Hour 24, 48, 72, 120 or Discharge (Whichever Comes First), and at Day 32 [0, 24, 48, 72, 120 hour or discharge; Day 32]

   Assess the effect of BMS-986231 on NT-proBNP (N-terminal prohormone of brain natriuretic peptide)

2. Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72 [Hours 6, 12, 24, 48, and 72]

   Endpoint was measured by the area under the curve (AUC) of the 11-point Numerical Rating Scale (NRS) obtained at baseline, and Hours 6, 12, 24, 48, and 72. Participants were asked to report their absolute current severity of dyspnea on an 11-point numerical rating scale (NRS; range 0 to 10). The numerical rating scale (NRS) was used to assess the degree of dyspnea (breathlessness), measured using an 11-point scale provided by the Sponsor. A score of 0 represents "I am not breathless at all" and 10 represents "I am the most breathless I can possibly imagine".

3. Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion [From start of infusion up to 6 hours post end of infusion]

   The percentage of participants experiencing symptoms of hypotension up to 6 hours post-treatment was reported for each arm.

4. Percentage of Participants With SBP < 90 mm Hg (Confirmed by a Repeated Value) [From start of infusion up to 6 hours post end of infusion]

   The percentage of participants experiencing SBP < 90 mm Hg (confirmed by a repeated value) up to 6 hours post-treatment was reported for each arm.

5. Number of Participants With a Serious Adverse Events (SAE) Assessed up to Day 32 [32 days]

   Number of participants who experienced an in-study SAE. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment.

6. Number of Participants Who Discontinued Due to Hypotension [up to 120 hours (for AEs); up to 32 days (for SAEs)]

   Number of participants who discontinued study treatment due to hypotension. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment. Hypotension defined as systolic blood pressure (SBP) < 90 mmHg.

7. Number of Participants Who Discontinued, Experienced a Down-titration or Dose Interruption Due to Decreased Blood Pressure [up to 120 hours (for AEs); up to 32 days (for SAEs)]

   Number of participants who discontinued study treatment, experienced a down-titration (dose reduction) or dose interruption due to decreased blood pressure/hypotension are reported below. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment. If the participant experienced systolic blood pressure (SBP) < 95 mm Hg, without symptoms related to hypotension, the measurement was repeated within 15 minutes. If the SBP remained < 95 mm Hg, the dose reduction occurred.

8. Number of Participants With an Adverse Event (AE) Assessed up to 120 Hours [up to 120 hours]

   Number of participants who experienced an in-study AE. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment.

9. Number of Participants Who Died (All- Cause and Cardiovascular-related) Through Day 182 [through 182 days]

   Number of participants who died (all- cause and CV related) through Day 182. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 CV=Cardiovascular

10. Change in Troponin T From Baseline to Hour 24, 48, and 72 [from baseline to Hour 24, 48, and 72]

    Baseline = Last non-missing result with a collection date-time less than or on the date-time of the start of infusion of study drug

11. Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Hematology [to 120 hours]

    Number of participants who experienced an in-study Hematology marked laboratory abnormality (reported in > 5% of total participants). Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0

12. Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Chemistry [to 120 hours]

    Number of participants who experienced an in-study Chemistry marked laboratory abnormality (reported in > 5% of total participants). Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0

13. Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Urinalysis [to 120 hours]

    Number of participants who experienced an in-study Urinalysis marked laboratory abnormality (reported in > 5% of total participants). Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0

14. Change in Vital Signs From Baseline to 120 Hours - Blood Pressure [to 120 hours]

    The change in baseline for vital signs was reported for each arm.

15. Change in Vital Signs From Baseline to 120 Hours - Heart Rate [to 120 hours]

    The change in baseline for vital signs was reported for each arm.

16. Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate [to 120 hours]

    The change in baseline for vital signs was reported for each arm.

17. Change in Vital Signs From Baseline to 120 Hours - Temperature [to 120 hours]

    The change in baseline for vital signs was reported for each arm.

18. Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate [to 120 hours]

    The change in baseline for ECGs was reported for each arm.

19. Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - PR, QT, QTcF Intervals and QRS Duration [to 120 hours]

    The change in baseline for ECGs was reported for each arm.

20. Change in Physical Measurements From Baseline to 120 Hours [to 120 hours]

    The change in baseline for physical measurements was reported for each arm.

21. Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^9 Cells/L [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.

22. Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - g/L [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.

23. Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mmol/L [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.

24. Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - U/L [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.

25. Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mg/dL [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.

26. Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^12 c/L [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.

27. Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Protein (Nmol/L) [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.

28. Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Creatinine (µmol/L) [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.

29. Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Cystatin (mg/L) [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.

30. Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Potassium Excretion [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.

31. Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Sodium Excretion [to 120 hours]

    The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Actively being hospitalized for acute decompensated heart failure

• At least 1 administration of IV diuretic for the current episode

• Be randomized within 18 hours of first dose of IV diuretic for current episode for Part 1 Cohort 1, or 48 hours for first dose for Part II Cohort II

• Have shortness of breath at rest or with minimal exertion after administration of 1 dose of IV diuretic

• Have history of heart failure and a left ventricular ejection fraction (LVEF) ≤ 40%

Exclusion Criteria:

• Systolic blood pressure <105mm Hg or >160mm Hg or heart rate <50 or >130 bpm

• Have an active infection requiring IV anti-microbial treatment

• Be hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening

• Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening

• Suspected acute lung disease (e.g pneumonia or asthma) or severe chronic lung disease (e.g. severe chronic obstructive pulmonary disease, or pulmonary fibrosis)

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Sarver Heart Center	Tucson	Arizona	United States	85724
2	University of Florida	Gainesville	Florida	United States	32610
3	Tampa General Hospital	Tampa	Florida	United States	33606
4	Emory University	Atlanta	Georgia	United States	30322
5	Indiana University Health Methodist Hospital	Indianapolis	Indiana	United States	46202
6	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
7	DMC Detroit Receiving Hospital	Detroit	Michigan	United States	48201
8	Harper University Hospital	Detroit	Michigan	United States	48201
9	Henry Ford Health System	Detroit	Michigan	United States	48202
10	Sinai Grace Hospital	Detroit	Michigan	United States	48235
11	Saint Louis University	Saint Louis	Missouri	United States	63110
12	Washington University	Saint Louis	Missouri	United States	63110
13	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
14	Duke University Medical Center	Durham	North Carolina	United States	27710
15	University of Cincinnati	Cincinnati	Ohio	United States	45267
16	Wexner Medical Center at The Ohio State University	Columbus	Ohio	United States	43210
17	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
18	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
19	Medical University of South Carolina - PPDS	Charleston	South Carolina	United States	29425
20	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
21	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
22	Ben Taub General Hospital	Houston	Texas	United States	77030
23	University of Utah Medical Center	Salt Lake City	Utah	United States	84132
24	University of Virginia Health System	Charlottesville	Virginia	United States	22908
25	Local Institution	Caba	Buenos Aires	Argentina	C1428ART
26	Local Institution	Rosario	Santa FE	Argentina	Santa Fe, 2000
27	Local Institution	Buenos Aires		Argentina
28	Local Institution	Cordoba		Argentina	5000
29	Local Institution	Cordoba		Argentina	X5000AAX
30	Local Institution	Cordoba		Argentina	X5000EPU
31	Local Institution	Cordoba		Argentina	X5000JHQ
32	Local Institution	Cordoba		Argentina
33	Local Institution	Corrientes		Argentina	3400
34	Local Institution	Santa Fe		Argentina	3000
35	Local Institution	Edmonton	Alberta	Canada	T6G 2R3
36	Local Institution	Halifax	Nova Scotia	Canada	B3H 4S9
37	Local Institution	Quebec		Canada	G1V 4G5
38	Local Institution	Brno		Czechia	625 00
39	Local Institution	Brno		Czechia	656 91
40	Local Institution	Hradec Kralove		Czechia	500 05
41	Local Institution	Plzen-Bory		Czechia	305 99
42	Local Institution	Prague		Czechia	12808
43	Local Institution	Praha 4		Czechia	140 21
44	Local Institution	Slany		Czechia	274 01
45	Local Institution	Besancon		France	25000
46	Local Institution	Beziers		France	34500
47	Local Institution	Bobigny		France	93009
48	Local Institution	Creteil		France
49	Local Institution	Evreux		France	27015
50	Local Institution	La Tronche		France	38700
51	Local Institution	Paris Cedex 10		France	75475
52	Local Institution	Paris		France	75013
53	Local Institution	Bad Nauheim		Germany	61231
54	Local Institution	Frankfurt		Germany	60590
55	Local Institution	Gottingen		Germany	37075
56	Local Institution	Greifswald		Germany
57	Local Institution	Hamburg		Germany	20246
58	Local Institution	Hannover		Germany	30625
59	Local Institution	Homburg		Germany	66421
60	Local Institution	Ludwigshafen		Germany	67063
61	Local Institution	Mainz		Germany
62	Local Institution	Regensburg		Germany	935053
63	Local Institution	Athens, Attiki		Greece	11527
64	Local Institution	Athens		Greece	11527
65	Local Institution	Athens		Greece	12464
66	Local Institution	Athens		Greece	14233
67	Local Institution	Ioannina		Greece	45500
68	Local Institution	Kallithea		Greece	17674
69	Local Institution	Larisa		Greece	41110
70	Local Institution	Thessaloniki		Greece	54636
71	Local Institution	Brescia		Italy	25123
72	Local Institution	Ferrara		Italy	44121
73	Local Institution	Foggia		Italy	71121
74	Local Institution	Nagoya-shi	Aichi	Japan	4678602
75	Local Institution	Seto	Aichi	Japan	489-0065
76	Local Institution	Fukushima-shi	Fukushima	Japan	9601295
77	Local Institution	Sapporo-shi	Hokkaido	Japan	0608648
78	Local Institution	Amagasaki	Hyogo	Japan	6608550
79	Local Institution	Sagamihara-shi	Kanagawa	Japan	2520375
80	Local Institution	Yokohama	Kanagawa	Japan	227-8501
81	Local Institution	Yokohama	Kanagawa	Japan	232-0024
82	Local Institution	Okayama-shi	Okayama	Japan	7008558
83	Local Institution	Suita-shi	Osaka	Japan
84	Local Institution	Kawaguchi	Saitama	Japan	333-0842
85	Local Institution	Bunkyo-ku	Tokyo	Japan	1138431
86	Local Institution	Bunkyo-ku	Tokyo	Japan	1138603
87	Local Institution	Itabashi-ku	Tokyo	Japan	1738610
88	Local Institution	Osaka		Japan	558-8558
89	Local Institution	Tokyo		Japan	113-8655
90	Local Institution	Tokyo		Japan	162-8655
91	Local Institution	Amersfoort		Netherlands	3818 ES
92	Local Institution	Deventer		Netherlands	7416 SE
93	Local Institution	Hardenberg		Netherlands	7772 SE
94	Local Institution	Leeuwarden		Netherlands	8934 AD
95	Local Institution	Bialystok		Poland	15-276
96	Local Institution	Katowice		Poland	40-635
97	Local Institution	Krakow		Poland	31-202
98	Local Institution	Lodz		Poland	91-347
99	Local Institution	Lodz		Poland	92-213
100	Local Institution	Warszawa		Poland	04-628
101	Local Institution	Wroclaw		Poland	50-981
102	Local Institution	Wroclaw		Poland	54-049
103	Local Institution	Zamosc		Poland	22-400
104	Local Institution	Alicante		Spain	03010
105	Local Institution	Barcelona		Spain	08025
106	Local Institution	Barcelona		Spain	8035
107	Local Institution	L'Hospitalet de Llobregat		Spain	08907
108	Local Institution	Madrid		Spain	28007
109	Local Institution	Madrid		Spain	28041
110	Local Institution	Sant Joan Despi		Spain	08970
111	Local Institution	Santiago De Compostela		Spain	15706
112	Local Institution	Belfast		United Kingdom	BT16 1RH
113	Local Institution	Blackpool		United Kingdom	FY3 8NR
114	Local Institution	Glasgow		United Kingdom	G4 0SF
115	Local Institution	Glasgow		United Kingdom	G51 4TF
116	Local Institution	London		United Kingdom	SW17 0QT

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 21, 2017
• Study Protocol - Apr 9, 2018

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03016325
• Other Study ID Numbers: CV013-011; 2016-001685-29
• First Posted: Jan 10, 2017
• Last Update Posted: Jan 6, 2021
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Pre-assignment Detail

Main study cohorts: 100 participants in Part I and 222 in Part II were assigned to treatment (322 randomized in total), of which 97 and 214, respectively, were treated (311 total treated). Reasons not treated (Part I): 3 other reasons. Reasons not treated (Part II): 2 no longer met study criteria; 1 adverse event (AE); 5 other reasons. Japanese-specific cohort: 18 participants were randomized and treated in Part II (Japan cohort)

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Period Title: Treatment Period
STARTED	48	49	71	71	72	6	6	6
COMPLETED	48	48	70	71	70	6	6	6
NOT COMPLETED	0	1	1	0	2	0	0	0
Period Title: Treatment Period
STARTED	48	49	71	71	72	6	6	6
COMPLETED	44	47	62	63	64	6	5	6
NOT COMPLETED	4	2	9	8	8	0	1	0
Period Title: Treatment Period
STARTED	48	49	71	71	72	6	6	6
COMPLETED	44	45	60	58	60	1	2	1
NOT COMPLETED	4	4	11	13	12	5	4	5

Baseline Characteristics

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)	Total
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants	Total of all reporting groups
Overall Participants	48	49	71	71	72	6	6	6	329
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.0 (12.23)	64.6 (12.23)	67.3 (11.52)	69.2 (11.41)	70.0 (11.52)	65.3 (17.88)	69.5 (13.31)	76.7 (10.48)	67.9 (11.94)
Age, Customized (Count of Participants)
< 65 years	17 35.4%	24 49%	21 29.6%	23 32.4%	19 26.4%	3 50%	3 50%	1 16.7%	111 33.7%
65 -to <=75 years	22 45.8%	15 30.6%	36 50.7%	26 36.6%	30 41.7%	0 0%	1 16.7%	2 33.3%	132 40.1%
>75 years	9 18.8%	10 20.4%	14 19.7%	22 31%	23 31.9%	3 50%	2 33.3%	3 50%	86 26.1%
Sex: Female, Male (Count of Participants)
Female	8 16.7%	10 20.4%	18 25.4%	20 28.2%	15 20.8%	0 0%	1 16.7%	2 33.3%	74 22.5%
Male	40 83.3%	39 79.6%	53 74.6%	51 71.8%	57 79.2%	6 100%	5 83.3%	4 66.7%	255 77.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2%	9 12.7%	11 15.5%	11 15.3%	0 0%	0 0%	0 0%	32 9.7%
Not Hispanic or Latino	44 91.7%	45 91.8%	18 25.4%	23 32.4%	20 27.8%	0 0%	0 0%	0 0%	150 45.6%
Unknown or Not Reported	4 8.3%	3 6.1%	44 62%	37 52.1%	41 56.9%	6 100%	6 100%	6 100%	147 44.7%
Race/Ethnicity, Customized (Count of Participants)
White	35 72.9%	37 75.5%	63 88.7%	62 87.3%	66 91.7%	0 0%	0 0%	0 0%	263 79.9%
Black or African American	11 22.9%	11 22.4%	4 5.6%	7 9.9%	4 5.6%	0 0%	0 0%	0 0%	37 11.2%
Asian	0 0%	0 0%	2 2.8%	2 2.8%	2 2.8%	6 100%	6 100%	6 100%	24 7.3%
Other	2 4.2%	1 2%	2 2.8%	0 0%	0 0%	0 0%	0 0%	0 0%	5 1.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clinically Relevant Hypotension up to 6 Hours After the End of Study Drug Infusion
Description	Percentage of participants with clinically relevant hypotension, defined by systolic blood pressure (SBP) < 90 mm Hg (confirmed by a repeated value < 90 mm Hg) or symptoms of hypotension, up to 6 hours after the end of study drug infusion
Time Frame	From start of infusion up to 6 hours post end of infusion

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
clinically relevant hypotension	8.3 17.3%	20.4 41.6%	18.3 25.8%	21.1 29.7%	34.7 48.2%	0 0%	33.3 555%	50.0 833.3%
symptoms of hypotension	2.1 4.4%	6.1 12.4%	1.4 2%	2.8 3.9%	8.3 11.5%	0 0%	0 0%	0 0%
confirmed SBP < 90 mmHg	6.3 13.1%	20.4 41.6%	18.3 25.8%	21.1 29.7%	29.2 40.6%	0 0%	33.3 555%	50.0 833.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, clinically relevant hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	2.45
	Confidence Interval	(2-Sided) 95%; 0.83 to 14.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, clinically relevant hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, symptoms of hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	2.94
	Confidence Interval	(2-Sided) 95%; 0.31 to 75.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, symptoms of hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, confirmed SBP < 90 mmHg - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	3.27
	Confidence Interval	(2-Sided) 95%; 1.01 to 14.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), clinically relevant hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.58 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), clinically relevant hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), symptoms of hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95%; 0.18 to 54.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), symptoms of hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), confirmed SBP < 90 mmHg - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.58 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), clinically relevant hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 1.04 to 3.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), clinically relevant hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), symptoms of hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	5.92
	Confidence Interval	(2-Sided) 95%; 0.91 to 149.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), symptoms of hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), confirmed SBP < 90 mmHg - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.87 to 3.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II (Japan Cohort), BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II-Japan (low dose), clinically relevant hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II (Japan Cohort), BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II-Japan (low dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II (Japan Cohort), BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II-Japan (high dose), clinically relevant hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II (Japan Cohort), BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II-Japan (high dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in NT-proBNP From Baseline to Hour 24, 48, 72, 120 or Discharge (Whichever Comes First), and at Day 32
Description	Assess the effect of BMS-986231 on NT-proBNP (N-terminal prohormone of brain natriuretic peptide)
Time Frame	0, 24, 48, 72, 120 hour or discharge; Day 32

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
24 hour	-270.88 (400.320)	-364.46 (456.158)	-147.96 (452.239)	-340.74 (430.639)	-416.91 (503.825)	-129.70 (255.716)	-165.93 (185.910)	-397.60 (330.721)
48 hour	-405.06 (591.711)	-510.51 (592.734)	-210.87 (580.487)	-300.87 (725.268)	-472.32 (610.590)	-329.24 (646.985)	-251.73 (243.794)	-497.35 (725.286)
72 hour	-396.21 (675.761)	-373.86 (702.530)	-249.26 (655.999)	-118.86 (900.798)	-293.94 (685.681)	-433.08 (761.573)	9.89 (523.754)	-229.56 (809.850)
120 hour	-541.36 (773.006)	-409.53 (751.624)	-140.60 (1358.127)	-76.20 (993.110)	-390.21 (717.114)	-434.36 (659.528)	-379.06 (244.917)	-552.55 (824.009)
Day 32	-202.07 (799.169)	-91.61 (2254.397)	-321.73 (600.297)	-361.73 (782.881)	-476.86 (716.072)	-556.69 (1288.342)	-343.64 (377.590)	-706.11 (1111.877)

3. Secondary Outcome

Title	Change in Participant-reported Resting Dyspnea From Baseline Through Hour 72
Description	Endpoint was measured by the area under the curve (AUC) of the 11-point Numerical Rating Scale (NRS) obtained at baseline, and Hours 6, 12, 24, 48, and 72. Participants were asked to report their absolute current severity of dyspnea on an 11-point numerical rating scale (NRS; range 0 to 10). The numerical rating scale (NRS) was used to assess the degree of dyspnea (breathlessness), measured using an 11-point scale provided by the Sponsor. A score of 0 represents "I am not breathless at all" and 10 represents "I am the most breathless I can possibly imagine".
Time Frame	Hours 6, 12, 24, 48, and 72

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
6 hour	-1.5 (1.84)	-1.5 (1.64)	-1.1 (1.90)	-1.7 (1.94)	-1.7 (2.13)	-0.3 (1.03)	0.0 (2.90)	-1.3 (3.44)
12 hour	-2.1 (2.38)	-2.2 (1.73)	-1.7 (2.75)	-2.4 (2.38)	-2.0 (2.49)	-1.0 (1.79)	-0.2 (3.37)	-1.4 (4.22)
24 hour	-2.0 (2.50)	-2.1 (2.19)	-2.1 (2.82)	-2.9 (2.68)	-2.2 (2.42)	-0.8 (1.72)	-1.5 (3.02)	-1.2 (2.14)
48 hour	-2.8 (2.15)	-2.6 (2.51)	-2.8 (3.00)	-3.4 (2.44)	-2.8 (2.45)	-1.2 (1.47)	-0.8 (3.43)	-2.0 (1.67)
72 hour	-2.9 (2.23)	-3.7 (2.22)	-3.2 (3.19)	-3.9 (2.28)	-3.2 (2.73)	-1.2 (2.14)	-1.2 (3.19)	-2.0 (2.00)

4. Secondary Outcome

Title	Percentage of Participants With Symptomatic Hypotension up to 6 Hours After the End of Study Drug Infusion
Description	The percentage of participants experiencing symptoms of hypotension up to 6 hours post-treatment was reported for each arm.
Time Frame	From start of infusion up to 6 hours post end of infusion

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Number (95% Confidence Interval) [Percentage of participants]	2.1 4.4%	6.1 12.4%	1.4 2%	2.8 3.9%	8.3 11.5%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, symptoms of hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	2.94
	Confidence Interval	(2-Sided) 95%; 0.31 to 75.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, symptoms of hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), symptoms of hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95%; 0.18 to 54.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), symptoms of hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), symptoms of hypotension - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	5.92
	Confidence Interval	(2-Sided) 95%; 0.91 to 149.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), symptoms of hypotension - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With SBP < 90 mm Hg (Confirmed by a Repeated Value)
Description	The percentage of participants experiencing SBP < 90 mm Hg (confirmed by a repeated value) up to 6 hours post-treatment was reported for each arm.
Time Frame	From start of infusion up to 6 hours post end of infusion

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Number (95% Confidence Interval) [Percentage of participants]	6.3 13.1%	20.4 41.6%	18.3 25.8%	21.1 29.7%	29.2 40.6%	0 0%	33.3 555%	50.0 833.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, confirmed SBP < 90 mmHg - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	3.27
	Confidence Interval	(2-Sided) 95%; 1.01 to 14.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part I, BMS-986231 - Part I
	Comments
	Type of Statistical Test	Superiority
	Comments	Part I, confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), confirmed SBP < 90 mmHg - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.58 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 6 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (low dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), confirmed SBP < 90 mmHg - relative risk
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative risk from placebo
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.87 to 3.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II, BMS-986231 12 µg/kg/Min - Part II
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II (high dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II (Japan Cohort), BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II-Japan (low dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo - Part II (Japan Cohort), BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
	Comments
	Type of Statistical Test	Superiority
	Comments	Part II-Japan (high dose), confirmed SBP < 90 mmHg - relative difference
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative difference from placebo
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants With a Serious Adverse Events (SAE) Assessed up to Day 32
Description	Number of participants who experienced an in-study SAE. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment.
Time Frame	32 days

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Number [Participants]	11 22.9%	14 28.6%	23 32.4%	15 21.1%	15 20.8%	1 16.7%	0 0%	1 16.7%

7. Secondary Outcome

Title	Number of Participants Who Discontinued Due to Hypotension
Description	Number of participants who discontinued study treatment due to hypotension. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment. Hypotension defined as systolic blood pressure (SBP) < 90 mmHg.
Time Frame	up to 120 hours (for AEs); up to 32 days (for SAEs)

Outcome Measure Data

Analysis Population Description

All treated participants Note: Discontinuation due to hypotension occurred per protocol-mandated lowering of blood pressure to < 90 mmHg.

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Number [Participants]	4 8.3%	8 16.3%	7 9.9%	13 18.3%	16 22.2%	0 0%	1 16.7%	3 50%

8. Secondary Outcome

Title	Number of Participants Who Discontinued, Experienced a Down-titration or Dose Interruption Due to Decreased Blood Pressure
Description	Number of participants who discontinued study treatment, experienced a down-titration (dose reduction) or dose interruption due to decreased blood pressure/hypotension are reported below. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment. If the participant experienced systolic blood pressure (SBP) < 95 mm Hg, without symptoms related to hypotension, the measurement was repeated within 15 minutes. If the SBP remained < 95 mm Hg, the dose reduction occurred.
Time Frame	up to 120 hours (for AEs); up to 32 days (for SAEs)

Outcome Measure Data

Analysis Population Description

All treated participants Note: Discontinuation due to decreased blood pressure occurred per protocol-mandated lowering of blood pressure to < 95 mmHg.

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
discontinuation	4 8.3%	8 16.3%	7 9.9%	13 18.3%	15 20.8%	0 0%	1 16.7%	3 50%
down-titration	3 6.3%	9 18.4%	9 12.7%	10 14.1%	25 34.7%	0 0%	1 16.7%	3 50%
interruption	3 6.3%	4 8.2%	4 5.6%	12 16.9%	13 18.1%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With an Adverse Event (AE) Assessed up to 120 Hours
Description	Number of participants who experienced an in-study AE. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 Included nonserious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment.
Time Frame	up to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Number [Participants]	31 64.6%	39 79.6%	48 67.6%	48 67.6%	55 76.4%	2 33.3%	6 100%	6 100%

10. Secondary Outcome

Title	Number of Participants Who Died (All- Cause and Cardiovascular-related) Through Day 182
Description	Number of participants who died (all- cause and CV related) through Day 182. Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0 CV=Cardiovascular
Time Frame	through 182 days

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
All-cause	3 6.3%	3 6.1%	11 15.5%	12 16.9%	9 12.5%	0 0%	0 0%	1 16.7%
CV-related	3 6.3%	2 4.1%	9 12.7%	10 14.1%	4 5.6%	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	Change in Troponin T From Baseline to Hour 24, 48, and 72
Description	Baseline = Last non-missing result with a collection date-time less than or on the date-time of the start of infusion of study drug
Time Frame	from baseline to Hour 24, 48, and 72

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
24 hour	4.11 (27.303)	-1.31 (12.278)	-1.80 (11.266)	-3.45 (20.030)	-8.09 (37.864)	-4.67 (3.983)	1.33 (5.750)	-7.67 (16.669)
48 hour	-0.93 (22.714)	14.56 (81.979)	-2.88 (16.424)	8.08 (71.672)	-11.15 (45.495)	-10.67 (10.633)	49.50 (118.417)	-8.40 (25.501)
72 hour	6.07 (30.033)	6.76 (66.673)	-1.44 (16.472)	5.00 (65.766)	-13.05 (68.276)	-10.50 (12.145)	248.00 (433.581)	-15.00 (25.169)

12. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Hematology
Description	Number of participants who experienced an in-study Hematology marked laboratory abnormality (reported in > 5% of total participants). Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
high leukocyte counts	5 10.4%	2 4.1%	5 7%	4 5.6%	3 4.2%	0 0%	0 0%	0 0%
low hemoglobin values	4 8.3%	5 10.2%	5 7%	6 8.5%	4 5.6%	1 16.7%	1 16.7%	0 0%
low platelet values	4 8.3%	2 4.1%	2 2.8%	7 9.9%	1 1.4%	0 0%	0 0%	0 0%
low neutrophils values	0 0%	1 2%	1 1.4%	1 1.4%	0 0%	0 0%	0 0%	0 0%
low leukocyte counts	0 0%	1 2%	2 2.8%	0 0%	0 0%	0 0%	0 0%	0 0%
low hematocrit values	1 2.1%	1 2%	1 1.4%	3 4.2%	0 0%	0 0%	0 0%	0 0%
low erythrocytes values	1 2.1%	1 2%	1 1.4%	3 4.2%	0 0%	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Chemistry
Description	Number of participants who experienced an in-study Chemistry marked laboratory abnormality (reported in > 5% of total participants). Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
high blood urea nitrogen values	23 47.9%	16 32.7%	23 32.4%	23 32.4%	18 25%	0 0%	1 16.7%	2 33.3%
high urate values	10 20.8%	15 30.6%	10 14.1%	20 28.2%	8 11.1%	0 0%	1 16.7%	1 16.7%
high potassium values	2 4.2%	5 10.2%	6 8.5%	7 9.9%	2 2.8%	0 0%	1 16.7%	0 0%
high alanine aminotransferase (ALT) values	6 12.5%	1 2%	5 7%	2 2.8%	2 2.8%	0 0%	0 0%	0 0%
high alkaline phosphatase values	5 10.4%	0 0%	2 2.8%	0 0%	1 1.4%	0 0%	0 0%	0 0%
low protein values	3 6.3%	9 18.4%	3 4.2%	8 11.3%	4 5.6%	0 0%	1 16.7%	0 0%
high asparate aminotransferase values	4 8.3%	0 0%	4 5.6%	2 2.8%	1 1.4%	0 0%	0 0%	0 0%
high bilirubin values	2 4.2%	2 4.1%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%
high bicarbonate values	1 2.1%	2 4.1%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
low chloride counts	1 2.1%	2 4.1%	1 1.4%	4 5.6%	1 1.4%	0 0%	0 0%	0 0%
high creatine kinase values	0 0%	1 2%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
high protein values	1 2.1%	0 0%	2 2.8%	0 0%	2 2.8%	0 0%	0 0%	0 0%
high sodium values	0 0%	1 2%	2 2.8%	0 0%	0 0%	0 0%	0 0%	0 0%
low bicarbonate values	0 0%	0 0%	2 2.8%	1 1.4%	1 1.4%	0 0%	0 0%	0 0%
low sodium values	0 0%	0 0%	0 0%	2 2.8%	0 0%	0 0%	0 0%	0 0%
low albumin values	0 0%	0 0%	0 0%	1 1.4%	2 2.8%	0 0%	0 0%	0 0%
low calcium values	0 0%	0 0%	2 2.8%	1 1.4%	2 2.8%	0 0%	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Marked Laboratory Abnormality Assessed to 120 Hours - Urinalysis
Description	Number of participants who experienced an in-study Urinalysis marked laboratory abnormality (reported in > 5% of total participants). Medical Dictionary for Regulatory Activities (MedDRA) version: 22.0
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
high protein values	10 20.8%	11 22.4%	16 22.5%	13 18.3%	17 23.6%	2 33.3%	2 33.3%	2 33.3%
high erythrocyte values	1 2.1%	1 2%	1 1.4%	3 4.2%	2 2.8%	0 0%	0 0%	0 0%
high leukocytes values	0 0%	1 2%	0 0%	2 2.8%	1 1.4%	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Change in Vital Signs From Baseline to 120 Hours - Blood Pressure
Description	The change in baseline for vital signs was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants with a 120-hour evaluation

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	29	26	50	48	44	6	6	6
systolic blood pressure, mmHg	-6.8 (16.60)	0.0 (17.75)	-4.3 (15.23)	-7.9 (15.60)	-8.8 (14.01)	-10.3 (15.60)	-17.5 (9.14)	-6.2 (16.44)
diastolic blood pressure, mmHg	-4.0 (12.67)	-1.9 (13.53)	-4.4 (12.99)	-3.4 (14.37)	-1.6 (10.83)	1.7 (16.24)	-15.7 (19.08)	-9.3 (14.45)

16. Secondary Outcome

Title	Change in Vital Signs From Baseline to 120 Hours - Heart Rate
Description	The change in baseline for vital signs was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Mean (Standard Deviation) [beats/min]	-1.8 (15.53)	-9.1 (17.13)	-8.3 (15.55)	-4.6 (15.40)	-6.3 (15.60)	-6.7 (21.88)	-3.0 (13.31)	3.8 (11.55)

17. Secondary Outcome

Title	Change in Vital Signs From Baseline to 120 Hours - Respiratory Rate
Description	The change in baseline for vital signs was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Mean (Standard Deviation) [breaths/min]	-2.6 (3.93)	-3.0 (4.82)	-2.9 (3.80)	-2.6 (4.33)	-1.8 (3.96)	-2.3 (2.88)	0.0 (9.98)	-1.4 (3.58)

18. Secondary Outcome

Title	Change in Vital Signs From Baseline to 120 Hours - Temperature
Description	The change in baseline for vital signs was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Mean (Standard Deviation) [degrees C]	-0.04 (0.643)	0.09 (0.649)	0.04 (0.427)	0.00 (0.342)	-0.05 (0.481)	-0.47 (0.650)	-0.27 (0.535)	0.44 (0.541)

19. Secondary Outcome

Title	Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - Mean Heart Rate
Description	The change in baseline for ECGs was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	5	6	6
Mean (Standard Deviation) [beats/min]	-5.3 (9.36)	-6.8 (21.31)	-7.1 (17.46)	-5.1 (18.64)	-6.1 (17.33)	2.0 (10.72)	-13.0 (12.62)	-5.2 (14.85)

20. Secondary Outcome

Title	Change in Electrocardiograms (ECGs) From Baseline to 120 Hours - PR, QT, QTcF Intervals and QRS Duration
Description	The change in baseline for ECGs was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
PR Interval, Aggregate, msec	-17.4 (66.31)	-2.3 (32.11)	-0.1 (23.49)	10.9 (22.02)	2.0 (25.41)	-1.5 (16.50)	10.4 (26.32)	6.0 (30.10)
QRS Duration, Aggregate, msec	5.1 (22.19)	-0.1 (12.46)	1.6 (20.29)	-1.6 (13.22)	2.7 (16.77)	-3.0 (4.80)	-2.5 (7.20)	3.0 (4.38)
QT Interval, Aggregate, msec	-10.6 (49.20)	7.2 (48.25)	8.7 (53.17)	5.8 (42.19)	-0.3 (45.39)	-30.0 (28.17)	5.7 (24.41)	16.5 (50.22)
QTcF Interval, Aggregate, msec	-27.5 (41.79)	-13.9 (41.56)	-4.0 (51.04)	-4.0 (33.59)	-10.3 (37.63)	-24.8 (20.00)	-8.8 (22.35)	3.2 (22.93)

21. Secondary Outcome

Title	Change in Physical Measurements From Baseline to 120 Hours
Description	The change in baseline for physical measurements was reported for each arm.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	48	49	71	71	72	6	6	6
Mean (Standard Deviation) [kg]	0.00 (0383)	0.10 (0.285)	-2.87 (4.447)	-2.96 (4.231)	-1.83 (5.295)	-3.58 (2.182)	-3.97 (2.160)	-6.08 (4.009)

22. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^9 Cells/L
Description	The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants with a 120-hour evaluation

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours
Measure Participants	30	23	41	36	39
leukocyte, x10^9 c/L	0.12 (3.078)	-1.38 (1.892)	-0.20 (4.370)	0.20 (2.549)	-0.09 (1.980)
platelet, x10^9 c/L	5.63 (31.679)	-5.77 (34.666)	1.84 (40.808)	3.26 (37.888)	1.26 (31.135)

23. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - g/L
Description	The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants with a 120-hour evaluation

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours
Measure Participants	30	23	46	42	43
hemoglobin, g/L	-0.67 (11.851)	-0.70 (8.573)	1.20 (11.487)	0.94 (11.684)	1.38 (9.161)
protein, g/L	1.10 (6.172)	2.77 (5.839)	0.57 (8.178)	0.38 (6.048)	-0.05 (5.367)

24. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mmol/L
Description	The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours
Measure Participants	48	49	71	71	72
blood urea nitrogen, mmol/L	4.01 (5.474)	0.32 (3.164)	1.96 (3.920)	2.15 (5.016)	1.24 (3.655)
urate, mmol/L	0.06 (0.154)	0.01 (0.108)	-0.01 (0.126)	0.04 (0.147)	-0.03 (0.111)
potassium, mmol/L	0.19 (0.697)	0.28 (0.513)	0.21 (0.692)	0.13 (0.558)	0.15 (0.651)

25. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - U/L
Description	The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours
Measure Participants	48	49	71	71	72
alanine aminotransferase (ALT), U/L	148.13 (837.833)	-2.73 (11.089)	-3.22 (102.038)	30.36 (189.310)	-13.07 (76.357)
alkaline phosphatase, U/L	-1.00 (28.018)	1.65 (11.052)	-1.31 (25.186)	5.43 (26.007)	-0.49 (21.474)
asparate aminotransferase, U/L	214.77 (1204.410)	-2.77 (10.277)	-11.15 (127.903)	10.81 (65.009)	-10.00 (52.075)

26. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - mg/dL
Description	The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours
Measure Participants	48	49	71	71	72
Mean (Standard Deviation) [mg/dL]	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

27. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Main Study Cohorts Only - x10^12 c/L
Description	The change in baseline for laboratory assessments was reported for each arm of the Main study cohorts only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part I	BMS-986231 - Part I	Placebo - Part II	BMS-986231 6 µg/kg/Min - Part II	BMS-986231 12 µg/kg/Min - Part II
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours	BMS-986231 dose of 6 µg/kg/min for 48 hours	BMS-986231 dose of 12 µg/kg/min for 48 hours
Measure Participants	48	49	71	71	72
Mean (Standard Deviation) [x10^12 c/L]	-0.02 (0.394)	0.02 (0.305)	0.04 (0.409)	0.04 (0.481)	0.09 (0.337)

28. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Protein (Nmol/L)
Description	The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	6	6	5
Mean (Standard Deviation) [nmol/L]	79.38 (192.568)	74.13 (110.919)	131.64 (407.611)

29. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Creatinine (µmol/L)
Description	The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	6	6	5
Mean (Standard Deviation) [µmol/L]	4.33 (17.728)	-1.50 (6.775)	12.40 (23.891)

30. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Cystatin (mg/L)
Description	The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	6	6	5
Mean (Standard Deviation) [mg/L]	0.18 (0.268)	0.17 (0.150)	0.25 (0.077)

31. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Potassium Excretion
Description	The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	6	5	5
Mean (Standard Deviation) [Fractional Potassium Excretion percent]	4.88 (8.009)	-1.22 (4.926)	-12.34 (13.316)

32. Secondary Outcome

Title	Change in Laboratory Assessments From Baseline to 120 Hours, Japan Cohort Only - Percentage Fractional Sodium Excretion
Description	The change in baseline for laboratory assessments was reported for each arm of the Japan cohort only.
Time Frame	to 120 hours

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo - Part II (Japan Cohort)	BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)	BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants	BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
Measure Participants	6	6	5
Mean (Standard Deviation) [Fractional Sodium Excretion percent]	0.02 (2.076)	-2.62 (4.538)	-5.50 (7.984)

Adverse Events

Time Frame	Includes non-serious adverse events with onset time from the start of study treatment, up to and including 120 hours after the start of study treatment and serious adverse events with onset time from the start of study treatment, up to and including 32 days after the start of study treatment. Mortality data reported through 182 days post-treatment
Arm/Group Title	Placebo - Part I		BMS-986231 - Part I		Placebo - Part II		BMS-986231 6 µg/kg/Min - Part II		BMS-986231 12 µg/kg/Min - Part II		Placebo - Part II (Japan Cohort)		BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)		BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
Arm/Group Description	Escalating dose of placebo (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)		Escalating dose of BMS-986231 (3 µg/kg/min for 4 hours, then 6 µg/kg/min for another 4 hours, then 12 µg/kg/min for the remaining 40 hours)		Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours		BMS-986231 dose of 6 µg/kg/min for 48 hours		BMS-986231 dose of 12 µg/kg/min for 48 hours		Matching placebo dose of 6 µg/kg/min or 12 µg/kg/min for 48 hours for Japanese participants		BMS-986231 dose of 6 µg/kg/min for 48 hours for Japanese participants		BMS-986231 dose of 12 µg/kg/min for 48 hours for Japanese participants
All Cause Mortality
	Placebo - Part I		BMS-986231 - Part I		Placebo - Part II		BMS-986231 6 µg/kg/Min - Part II		BMS-986231 12 µg/kg/Min - Part II		Placebo - Part II (Japan Cohort)		BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)		BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/48 (6.3%)		3/49 (6.1%)		11/71 (15.5%)		12/71 (16.9%)		9/72 (12.5%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Serious Adverse Events
	Placebo - Part I		BMS-986231 - Part I		Placebo - Part II		BMS-986231 6 µg/kg/Min - Part II		BMS-986231 12 µg/kg/Min - Part II		Placebo - Part II (Japan Cohort)		BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)		BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/48 (22.9%)		14/49 (28.6%)		23/71 (32.4%)		15/71 (21.1%)		15/72 (20.8%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Cardiac disorders
CARDIAC FAILURE	2/48 (4.2%)		6/49 (12.2%)		8/71 (11.3%)		2/71 (2.8%)		7/72 (9.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ACUTE MYOCARDIAL INFARCTION	2/48 (4.2%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CARDIAC FAILURE CONGESTIVE	1/48 (2.1%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CARDIOGENIC SHOCK	1/48 (2.1%)		1/49 (2%)		3/71 (4.2%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CARDIORENAL SYNDROME	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
MYOCARDIAL INFARCTION	0/48 (0%)		1/49 (2%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ATRIOVENTRICULAR BLOCK COMPLETE	1/48 (2.1%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CARDIAC FAILURE ACUTE	1/48 (2.1%)		0/49 (0%)		0/71 (0%)		2/71 (2.8%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CORONARY ARTERY STENOSIS	1/48 (2.1%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ANGINA PECTORIS	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ATRIOVENTRICULAR BLOCK	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CARDIAC ARREST	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
PERICARDIAL EFFUSION	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VENTRICULAR FIBRILLATION	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CARDIAC FAILURE CHRONIC	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CORONARY ARTERY DISEASE	0/48 (0%)		0/49 (0%)		2/71 (2.8%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SINUS BRADYCARDIA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SUPRAVENTRICULAR TACHYCARDIA	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VENTRICULAR ARRHYTHMIA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VENTRICULAR TACHYCARDIA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
MYOCARDIAL ISCHAEMIA	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
General disorders
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Hepatobiliary disorders
HEPATIC CONGESTION	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Infections and infestations
ACINETOBACTER BACTERAEMIA	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
PNEUMONIA	0/48 (0%)		1/49 (2%)		0/71 (0%)		2/71 (2.8%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
BRONCHITIS	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CELLULITIS	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SEPTIC SHOCK	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
STAPHYLOCOCCAL SEPSIS	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ENDOCARDITIS	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ERYSIPELAS	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
WRIST FRACTURE	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Investigations
ELECTROCARDIOGRAM QRS COMPLEX PROLONGED	1/48 (2.1%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
HYPERNATRAEMIA	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
FLUID OVERLOAD	1/48 (2.1%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER CANCER	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Nervous system disorders
ALTERED STATE OF CONSCIOUSNESS	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Psychiatric disorders
CONFUSIONAL STATE	0/48 (0%)		1/49 (2%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
DELIRIUM	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ORGANIC BRAIN SYNDROME	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Renal and urinary disorders
ACUTE KIDNEY INJURY	3/48 (6.3%)		1/49 (2%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
BLADDER MASS	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
END STAGE RENAL DISEASE	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
RENAL FAILURE	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HYPERCAPNIA	0/48 (0%)		1/49 (2%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/48 (2.1%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
SLEEP APNOEA SYNDROME	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ACUTE PULMONARY OEDEMA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ASTHMA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
DYSPNOEA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
PULMONARY OEDEMA	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Vascular disorders
ANGIOPATHY	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HYPOTENSION	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
DEEP VEIN THROMBOSIS	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ILIAC ARTERY OCCLUSION	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
PERIPHERAL ARTERY OCCLUSION	0/48 (0%)		0/49 (0%)		1/71 (1.4%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo - Part I		BMS-986231 - Part I		Placebo - Part II		BMS-986231 6 µg/kg/Min - Part II		BMS-986231 12 µg/kg/Min - Part II		Placebo - Part II (Japan Cohort)		BMS-986231 6 µg/kg/Min - Part II (Japan Cohort)		BMS-986231 12 µg/kg/Min - Part II (Japan Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/48 (37.5%)		40/49 (81.6%)		47/71 (66.2%)		43/71 (60.6%)		54/72 (75%)		2/6 (33.3%)		6/6 (100%)		6/6 (100%)
Cardiac disorders
CARDIAC FAILURE	2/48 (4.2%)		6/49 (12.2%)		8/71 (11.3%)		2/71 (2.8%)		7/72 (9.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
VENTRICULAR TACHYCARDIA	3/48 (6.3%)		1/49 (2%)		2/71 (2.8%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
ATRIAL FIBRILLATION	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
MYOCARDIAL ISCHAEMIA	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Eye disorders
VITREOUS DETACHMENT	0/48 (0%)		0/49 (0%)		0/71 (0%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Gastrointestinal disorders
CONSTIPATION	2/48 (4.2%)		0/49 (0%)		1/71 (1.4%)		1/71 (1.4%)		0/72 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
DIARRHOEA	0/48 (0%)		1/49 (2%)		1/71 (1.4%)		1/71 (1.4%)		1/72 (1.4%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Infections and infestations
URINARY TRACT INFECTION	1/48 (2.1%)		2/49 (4.1%)		0/71 (0%)		3/71 (4.2%)		3/72 (4.2%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Investigations
BLOOD CREATININE INCREASED	0/48 (0%)		0/49 (0%)		0/71 (0%)		4/71 (5.6%)		0/72 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
HYPERURICAEMIA	1/48 (2.1%)		4/49 (8.2%)		3/71 (4.2%)		1/71 (1.4%)		2/72 (2.8%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
HYPOKALAEMIA	1/48 (2.1%)		3/49 (6.1%)		7/71 (9.9%)		8/71 (11.3%)		8/72 (11.1%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
HYPOGLYCAEMIA	1/48 (2.1%)		1/49 (2%)		0/71 (0%)		1/71 (1.4%)		2/72 (2.8%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS	2/48 (4.2%)		0/49 (0%)		0/71 (0%)		2/71 (2.8%)		1/72 (1.4%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Nervous system disorders
HEADACHE	1/48 (2.1%)		6/49 (12.2%)		5/71 (7%)		4/71 (5.6%)		2/72 (2.8%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
DIZZINESS	0/48 (0%)		3/49 (6.1%)		0/71 (0%)		0/71 (0%)		2/72 (2.8%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
TRANSIENT ISCHAEMIC ATTACK	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		2/72 (2.8%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Psychiatric disorders
INSOMNIA	2/48 (4.2%)		2/49 (4.1%)		6/71 (8.5%)		2/71 (2.8%)		1/72 (1.4%)		1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)
Renal and urinary disorders
ACUTE KIDNEY INJURY	3/48 (6.3%)		1/49 (2%)		1/71 (1.4%)		1/71 (1.4%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
RENAL IMPAIRMENT	3/48 (6.3%)		0/49 (0%)		3/71 (4.2%)		2/71 (2.8%)		1/72 (1.4%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
RASH PRURITIC	0/48 (0%)		0/49 (0%)		0/71 (0%)		0/71 (0%)		0/72 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Vascular disorders
HYPOTENSION	5/48 (10.4%)		14/49 (28.6%)		15/71 (21.1%)		20/71 (28.2%)		31/72 (43.1%)		0/6 (0%)		3/6 (50%)		4/6 (66.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.