Trial Outcomes & Findings for An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic (NCT NCT03730961)

NCT ID: NCT03730961

Last Updated: 2021-02-26

Results Overview

The total volume of urinary output 4 hours after 40 mg furosemide bolus given to participants with HFrEF while on BMS-986231 compared to placebo: absolute difference in total volume and % change from placebo. Sequence 1: Placebo in period 1, drug in period 2 Sequence 2: Drug in period 1, placebo in period 2

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: 4 hours
• Results posted on: 2021-02-26

Participant Flow

23 participants were randomized/assigned to treatment, and 23 initiated period 1 treatment.

Participant milestones

Measure	Sequence 1 First received placebo (period 1), then received BMS-986231 (period 2) following washout. Each treatment administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Sequence 2 First received BMS-986231 (period 1), then received placebo (period 2) following washout. Each treatment administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Overall Study STARTED	12	11
Overall Study Period 1 Completion	12	11
Overall Study Period 2 Completion	11	10
Overall Study COMPLETED	12	10
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Sequence 1 First received placebo (period 1), then received BMS-986231 (period 2) following washout. Each treatment administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Sequence 2 First received BMS-986231 (period 1), then received placebo (period 2) following washout. Each treatment administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Overall Study Adverse Event	0	1

Baseline Characteristics

An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic

Baseline characteristics by cohort

Measure	Sequence 1 n=12 Participants First received placebo (period 1), then received BMS-986231 (period 2) following washout. Each treatment administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Sequence 2 n=11 Participants First received BMS-986231 (period 1), then received placebo (period 2) following washout. Each treatment administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Age, Continuous	67.7 Years STANDARD_DEVIATION 8.19 • n=5 Participants	69.8 Years STANDARD_DEVIATION 8.23 • n=7 Participants	68.7 Years STANDARD_DEVIATION 8.10 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 hours

Population: Treated (per Protocol set) - All randomized participants who were given both study treatments and completed the study as per protocol. Participants are included in the treatment group they received in each period.

The total volume of urinary output 4 hours after 40 mg furosemide bolus given to participants with HFrEF while on BMS-986231 compared to placebo: absolute difference in total volume and % change from placebo.

Sequence 1: Placebo in period 1, drug in period 2

Sequence 2: Drug in period 1, placebo in period 2

Outcome measures

Measure	BMS-986231 n=21 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=21 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo Sequence 1	900.7 mL Standard Deviation 366.56	1603.3 mL Standard Deviation 674.18
4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo Sequence 2	1176.7 mL Standard Deviation 386.21	1345.4 mL Standard Deviation 391.11
4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo Total	1032.1 mL Standard Deviation 392.74	1480.5 mL Standard Deviation 559.92

SECONDARY outcome

Timeframe: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours

Population: All randomized subjects who started study drug infusion in at least one treatment period. This is also known as the Intent to Treat (ITT) population. Data in this data set was analyzed based on randomized sequence of treatments.

Secondary efficacy analyses was performed using the randomized population. The FeNa, FeK, furosemide urinary and plasma concentration and the ratio of urinary sodium to urinary furosemide was calculated at each time point over 4-hour urine/plasma collection after a bolus injection of 40 mg furosemide while receiving BMS-986231 or placebo.

Fractional Excretion Na = ((Urine Sodium * Plasma Creatinine) / (Plasma Sodium * Urine Creatinine)) * 100

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo Before start of infusion	0.5 percent of filtered sodium Standard Deviation 0.52	0.6 percent of filtered sodium Standard Deviation 0.73
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo 0-4 hours	0.6 percent of filtered sodium Standard Deviation 0.67	0.7 percent of filtered sodium Standard Deviation 0.84
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo 4-5 hours	4.6 percent of filtered sodium Standard Deviation 3.34	5.4 percent of filtered sodium Standard Deviation 3.09
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo 5-6 hours	5.0 percent of filtered sodium Standard Deviation 2.87	7.0 percent of filtered sodium Standard Deviation 3.51
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo 6-7 hours	3.3 percent of filtered sodium Standard Deviation 2.33	4.7 percent of filtered sodium Standard Deviation 2.79
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo 7-8 hours	1.7 percent of filtered sodium Standard Deviation 1.26	3.3 percent of filtered sodium Standard Deviation 2.52

SECONDARY outcome

Timeframe: Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours

Population: All randomized subjects who started study drug infusion in at least one treatment period. This is also known as the Intent to Treat (ITT) population. Data in this data set was analyzed based on randomized sequence of treatments.

Secondary efficacy analyses was performed using the randomized population. The FeNa, FeK, furosemide urinary and plasma concentration and the ratio of urinary sodium to urinary furosemide was calculated at each time point over 4-hour urine/plasma collection after a bolus injection of 40 mg furosemide while receiving BMS-986231 or placebo.

Fractional Excretion K = ((Urine Potassium * Plasma Creatinine) / (Plasma Potassium * Urine Creatinine)) * 100

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo Before start of infusion	0.4 percent of filtered potassium Standard Deviation 0.16	0.4 percent of filtered potassium Standard Deviation 0.17
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo 0-4 hours	0.5 percent of filtered potassium Standard Deviation 0.20	0.4 percent of filtered potassium Standard Deviation 0.17
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo 4-5 hours	1.1 percent of filtered potassium Standard Deviation 0.67	0.9 percent of filtered potassium Standard Deviation 0.46
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo 5-6 hours	1.2 percent of filtered potassium Standard Deviation 0.54	1.2 percent of filtered potassium Standard Deviation 0.52
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo 6-7 hours	1.1 percent of filtered potassium Standard Deviation 0.42	1.0 percent of filtered potassium Standard Deviation 0.35
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo 7-8 hours	1.0 percent of filtered potassium Standard Deviation 0.32	0.8 percent of filtered potassium Standard Deviation 0.32

SECONDARY outcome

Timeframe: Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours

Population: All randomized subjects who started study drug infusion in at least one treatment period. This is also known as the Intent to Treat (ITT) population. Data in this data set was analyzed based on randomized sequence of treatments.

Summary of urine recovery by interval, measured by amount excreted.

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Furosemide Urinary Concentrations Before start of infusion	0.2 mg Standard Deviation 0.13	0.2 mg Standard Deviation 0.11
Furosemide Urinary Concentrations 0-2 hours	0.1 mg Standard Deviation 0.08	0.1 mg Standard Deviation 0.11
Furosemide Urinary Concentrations 2-4 hours	0.3 mg Standard Deviation 0.37	0.1 mg Standard Deviation 0.11
Furosemide Urinary Concentrations 4-5 hours	7.9 mg Standard Deviation 4.66	8.2 mg Standard Deviation 4.56
Furosemide Urinary Concentrations 5-6 hours	4.3 mg Standard Deviation 1.74	3.7 mg Standard Deviation 1.48
Furosemide Urinary Concentrations 6-7 hours	2.8 mg Standard Deviation 2.03	2.7 mg Standard Deviation 1.43
Furosemide Urinary Concentrations 7-8 hours	2.0 mg Standard Deviation 1.22	1.7 mg Standard Deviation 1.15
Furosemide Urinary Concentrations 8-10 hours	1.7 mg Standard Deviation 1.28	1.6 mg Standard Deviation 1.00

SECONDARY outcome

Timeframe: Day 1: 4, 5, 6, 8, 10 hours

Population: All randomized subjects who started study drug infusion in at least one treatment period. This is also known as the Intent to Treat (ITT) population. Data in this data set was analyzed based on randomized sequence of treatments.

Summary of plasma concentrations by interval.

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Furosemide Plasma Concentrations 4 hours post-dose	1605 ng/mL Standard Deviation 5384	63.6 ng/mL Standard Deviation 140.3
Furosemide Plasma Concentrations 5 hours post-dose	2049 ng/mL Standard Deviation 593.0	2145 ng/mL Standard Deviation 653.2
Furosemide Plasma Concentrations 6 hours post-dose	1122 ng/mL Standard Deviation 437.6	1146 ng/mL Standard Deviation 466.8
Furosemide Plasma Concentrations 8 hours post-dose	426.8 ng/mL Standard Deviation 204.8	476.6 ng/mL Standard Deviation 226.0
Furosemide Plasma Concentrations 10 hours post-dose	345.6 ng/mL Standard Deviation 386.6	244.3 ng/mL Standard Deviation 164.3

SECONDARY outcome

Timeframe: 0-4 hours after furosemide

Population: Treated (per Protocol set) - All randomized participants who were given both study treatments and completed the study as per protocol. Participants are included in the treatment group they received in each period.

Summary of urinary concentrations 0-4 hours after furosemide

Ratio = Cumulative Sodium Excretion / Cumulative Furosemide in Urine

Outcome measures

Measure	BMS-986231 n=21 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=21 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion	6.1 Ratio of Urinary Na:Urinary furosemide Standard Deviation 3.18	10.1 Ratio of Urinary Na:Urinary furosemide Standard Deviation 4.74

SECONDARY outcome

Timeframe: up to 8 hours

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Number of Participants With Clinically Relevant Hypotension	4 Number of participants	0 Number of participants

SECONDARY outcome

Timeframe: up to 8 days

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Number of Participants With an Adverse Event (AE)	8 Number of participants	6 Number of participants

SECONDARY outcome

Timeframe: from first dose to 30 days post-last dose (ca. 5-8 weeks)

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

Number of participants who experienced an in-study abnormal clinical laboratory event under the category of Hematology, Chemistry or Urinalysis.

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Number of Participants With an Abnormal Clinical Laboratory Value	0 Number of participants	0 Number of participants

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose (end of infusion)

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

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

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=22 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Change From Baseline in Vital Signs - Blood Pressure diastolic blood pressure	-14.5 mmHg Standard Deviation 9.99	-0.6 mmHg Standard Deviation 10.46
Change From Baseline in Vital Signs - Blood Pressure systolic blood pressure	-28.4 mmHg Standard Deviation 15.60	-4.9 mmHg Standard Deviation 14.55

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose (end of infusion)

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

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

Outcome measures

Measure	BMS-986231 n=22 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=22 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Change From Baseline in Vital Signs - Heart Rate	0.5 beats/min Standard Deviation 10.40	-0.1 beats/min Standard Deviation 8.08

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose (end of infusion)

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

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

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=22 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Change From Baseline in Vital Signs - Oxygen Saturation	-1.0 oxygen saturation percentage Standard Deviation 1.82	0.0 oxygen saturation percentage Standard Deviation 1.56

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose (end of infusion)

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

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

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=21 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate	0.9 beats/min Standard Deviation 7.97	1.6 beats/min Standard Deviation 7.61

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose (end of infusion)

Population: Safety set : All randomized participants who take at least 1 dose of double-blind study treatment. Participants were included in the treatment group they received in each period.

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

Outcome measures

Measure	BMS-986231 n=23 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=21 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals PR Interval, Aggregate	2.0 msec Standard Deviation 24.21	-2.8 msec Standard Deviation 12.17
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals QRS Duration, Aggregate	-0.9 msec Standard Deviation 25.91	2.2 msec Standard Deviation 21.46
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals QT Interval, Aggregate	-9.1 msec Standard Deviation 27.88	-7.9 msec Standard Deviation 16.95
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals QTcF Interval, Aggregate	-11.2 msec Standard Deviation 26.90	-5.1 msec Standard Deviation 16.74

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose

Population: Analysis population is 0, data not collected

Telemetry data not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1, 8 hours post-dose (end of infusion)

Population: Treated (per Protocol set) - All randomized participants who were given both study treatments and completed the study as per protocol. Participants are included in the treatment group they received in each period.

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

Outcome measures

Measure	BMS-986231 n=20 Participants BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=19 Participants Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Change From Baseline in Physical Examination - Body Weight	0.2 kg Standard Deviation 0.77	-0.5 kg Standard Deviation 0.72

Adverse Events

BMS-986231

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	BMS-986231 n=23 participants at risk BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 participants at risk Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Cardiac disorders Myocardial infarction	4.3% 1/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Infections and infestations Lower respiratory tract infection	4.3% 1/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	4.3% 1/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	4.3% 1/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	4.3% 1/23 • From first dose to 100 days post-last dose (up to ca. 4 months)

Other adverse events

Measure	BMS-986231 n=23 participants at risk BMS-986231 administered 8 hours continuous IV infusion at the dose of 12 μg/kg/min, corresponding to an infusion rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.	Placebo n=23 participants at risk Placebo administered 8 hours continuous IV infusion of D5W administered at the flow rate of 20 mL/H. At hour 4 after the start of the infusion, 40 mg IV bolus of furosemide administered through a separate IV line, given slowly over 1 to 2 minutes.
Infections and infestations Lower respiratory tract infection	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	8.7% 2/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Nervous system disorders Dizziness	8.7% 2/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Nervous system disorders Headache	13.0% 3/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	4.3% 1/23 • From first dose to 100 days post-last dose (up to ca. 4 months)
Vascular disorders Hypotension	13.0% 3/23 • From first dose to 100 days post-last dose (up to ca. 4 months)	0.00% 0/23 • From first dose to 100 days post-last dose (up to ca. 4 months)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email:

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60