Cardiac Failure, Congestive Heart Failure, Heart Decompensation, Myocardial Failure
Conditions
Brief summary
The purpose of this study is to investigate continuous 8-hour introductions of BMS-986231 in participants with heart failure and weakened heart function given a standard dose of diuretic.
Interventions
DRUGBMS-986231
Intravenous administration
DRUGFurosemide
Intravenous administration
DRUGPlacebo
Intravenous administration
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Left ventricular ejection fraction \<45%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan within 18 months * On stable chronic guideline-directed therapy for HF including chronic loop diuretics, ACEi, ARBs, MRAs, ARNI or / and β-blockers as tolerated, with no changes of these medications in the past 2 weeks * At least an oral dose of 40 mg of furosemide/day or equivalent (20 mg torsemide, 1 mg bumetamide)
Exclusion criteria
* SBP \< 115 mm Hg or \> 180 mm Hg at screening or pre-randomization * Heart rate \< 50 beats per minute (bpm) or \> 120 bpm at screening or pre-randomization * Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo | 4 hours | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours | 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 |
| Furosemide Urinary Concentrations | Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours | Summary of urine recovery by interval, measured by amount excreted. |
| Furosemide Plasma Concentrations | Day 1: 4, 5, 6, 8, 10 hours | Summary of plasma concentrations by interval. |
| Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion | 0-4 hours after furosemide | Summary of urinary concentrations 0-4 hours after furosemide Ratio = Cumulative Sodium Excretion / Cumulative Furosemide in Urine |
| Number of Participants With Clinically Relevant Hypotension | up to 8 hours | Clinically relevant hypotension is defined as systolic blood pressure (SBP) \< 90 mmHg or symptomatic hypotension during infusion |
| Number of Participants With an Adverse Event (AE) | up to 8 days | Clinically relevant hypotension is defined as systolic blood pressure (SBP) \< 90 mmHg or symptomatic hypotension during infusion |
| Number of Participants With an Abnormal Clinical Laboratory Value | from first dose to 30 days post-last dose (ca. 5-8 weeks) | Number of participants who experienced an in-study abnormal clinical laboratory event under the category of Hematology, Chemistry or Urinalysis. |
| FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours | 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 |
| Change From Baseline in Vital Signs - Heart Rate | Day 1, 8 hours post-dose (end of infusion) | The change in baseline for vital signs was reported for each arm. |
| Change From Baseline in Vital Signs - Oxygen Saturation | Day 1, 8 hours post-dose (end of infusion) | The change in baseline for vital signs was reported for each arm. |
| Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate | Day 1, 8 hours post-dose (end of infusion) | The change in baseline for ECGs was reported for each arm. |
| Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | Day 1, 8 hours post-dose (end of infusion) | The change in baseline for ECGs was reported for each arm. |
| Telemetry | Day 1, 8 hours post-dose | Telemetry data not collected. |
| Change From Baseline in Physical Examination - Body Weight | Day 1, 8 hours post-dose (end of infusion) | The change in baseline for physical examinations was reported for each arm. |
| Change From Baseline in Vital Signs - Blood Pressure | Day 1, 8 hours post-dose (end of infusion) | The change in baseline for vital signs was reported for each arm. |
Countries
United Kingdom
Participant flow
Pre-assignment details
23 participants were randomized/assigned to treatment, and 23 initiated period 1 treatment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| 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. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 9 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 2 Participants | 8 Participants |
| Age, Continuous | 67.7 Years STANDARD_DEVIATION 8.19 | 69.8 Years STANDARD_DEVIATION 8.23 | 68.7 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 11 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 6 / 23 | 3 / 23 |
| serious Total, serious adverse events | 1 / 23 | 2 / 23 |
Outcome results
Primary
4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo
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
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| Placebo | 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo | Sequence 2 | 1345.4 mL | Standard Deviation 391.11 |
| Placebo | 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo | Sequence 1 | 1603.3 mL | Standard Deviation 674.18 |
| Placebo | 4-hour Urinary Output Following Intravenous Administration of 40 mg Furosemide to HFrEF Participants Receiving BMS-986231 Infusion Compared to Placebo | Total | 1480.5 mL | Standard Deviation 559.92 |
p-value: 0.002195% CI: [-714, -183]t-test, 2 sided
p-value: 0.022295% CI: [-40.7, -3.51]t-test, 2 sided
Secondary
Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate
The change in baseline for ECGs was reported for each arm.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS-986231 | Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate | 0.9 beats/min | Standard Deviation 7.97 |
| Placebo | Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate | 1.6 beats/min | Standard Deviation 7.61 |
Secondary
Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals
The change in baseline for ECGs was reported for each arm.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | PR Interval, Aggregate | 2.0 msec | Standard Deviation 24.21 |
| BMS-986231 | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | QRS Duration, Aggregate | -0.9 msec | Standard Deviation 25.91 |
| BMS-986231 | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | QT Interval, Aggregate | -9.1 msec | Standard Deviation 27.88 |
| BMS-986231 | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | QTcF Interval, Aggregate | -11.2 msec | Standard Deviation 26.9 |
| Placebo | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | QTcF Interval, Aggregate | -5.1 msec | Standard Deviation 16.74 |
| Placebo | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | PR Interval, Aggregate | -2.8 msec | Standard Deviation 12.17 |
| Placebo | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | QT Interval, Aggregate | -7.9 msec | Standard Deviation 16.95 |
| Placebo | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | QRS Duration, Aggregate | 2.2 msec | Standard Deviation 21.46 |
Secondary
Change From Baseline in Physical Examination - Body Weight
The change in baseline for physical examinations was reported for each arm.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS-986231 | Change From Baseline in Physical Examination - Body Weight | 0.2 kg | Standard Deviation 0.77 |
| Placebo | Change From Baseline in Physical Examination - Body Weight | -0.5 kg | Standard Deviation 0.72 |
Secondary
Change From Baseline in Vital Signs - Blood Pressure
The change in baseline for vital signs was reported for each arm.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | Change From Baseline in Vital Signs - Blood Pressure | diastolic blood pressure | -14.5 mmHg | Standard Deviation 9.99 |
| BMS-986231 | Change From Baseline in Vital Signs - Blood Pressure | systolic blood pressure | -28.4 mmHg | Standard Deviation 15.6 |
| Placebo | Change From Baseline in Vital Signs - Blood Pressure | diastolic blood pressure | -0.6 mmHg | Standard Deviation 10.46 |
| Placebo | Change From Baseline in Vital Signs - Blood Pressure | systolic blood pressure | -4.9 mmHg | Standard Deviation 14.55 |
Secondary
Change From Baseline in Vital Signs - Heart Rate
The change in baseline for vital signs was reported for each arm.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS-986231 | Change From Baseline in Vital Signs - Heart Rate | 0.5 beats/min | Standard Deviation 10.4 |
| Placebo | Change From Baseline in Vital Signs - Heart Rate | -0.1 beats/min | Standard Deviation 8.08 |
Secondary
Change From Baseline in Vital Signs - Oxygen Saturation
The change in baseline for vital signs was reported for each arm.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS-986231 | Change From Baseline in Vital Signs - Oxygen Saturation | -1.0 oxygen saturation percentage | Standard Deviation 1.82 |
| Placebo | Change From Baseline in Vital Signs - Oxygen Saturation | 0.0 oxygen saturation percentage | Standard Deviation 1.56 |
Secondary
FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo
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
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | 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 |
| BMS-986231 | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | 0-4 hours | 0.5 percent of filtered potassium | Standard Deviation 0.2 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| Placebo | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | 6-7 hours | 1.0 percent of filtered potassium | Standard Deviation 0.35 |
| Placebo | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | Before start of infusion | 0.4 percent of filtered potassium | Standard Deviation 0.17 |
| Placebo | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | 5-6 hours | 1.2 percent of filtered potassium | Standard Deviation 0.52 |
| Placebo | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | 0-4 hours | 0.4 percent of filtered potassium | Standard Deviation 0.17 |
| Placebo | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | 7-8 hours | 0.8 percent of filtered potassium | Standard Deviation 0.32 |
| Placebo | FeK in Participants With HFrEF While on BMS-986231 Compared to Placebo | 4-5 hours | 0.9 percent of filtered potassium | Standard Deviation 0.46 |
p-value: 0.162195% CI: [-0.189, 1.05]t-test, 2 sided
p-value: 0.033895% CI: [2.72, 61.3]t-test, 2 sided
p-value: 0.0695% CI: [-0.0353, 1.57]t-test, 2 sided
p-value: 0.02895% CI: [4.02, 63]t-test, 2 sided
Secondary
FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo
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
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| BMS-986231 | 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 |
| Placebo | FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | 6-7 hours | 4.7 percent of filtered sodium | Standard Deviation 2.79 |
| Placebo | FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | 5-6 hours | 7.0 percent of filtered sodium | Standard Deviation 3.51 |
| Placebo | FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | 7-8 hours | 3.3 percent of filtered sodium | Standard Deviation 2.52 |
| Placebo | FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | 4-5 hours | 5.4 percent of filtered sodium | Standard Deviation 3.09 |
| Placebo | FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | Before start of infusion | 0.6 percent of filtered sodium | Standard Deviation 0.73 |
| Placebo | FeNa in Participants With HFrEF While on BMS-986231 Compared to Placebo | 0-4 hours | 0.7 percent of filtered sodium | Standard Deviation 0.84 |
p-value: 0.016395% CI: [-7.63, -0.876]t-test, 2 sided
p-value: 0.201895% CI: [-38.8, 8.77]t-test, 2 sided
p-value: 0.052695% CI: [-7.27, 0.0446]t-test, 2 sided
p-value: 0.207695% CI: [-38.8, 9]t-test, 2 sided
Secondary
Furosemide Plasma Concentrations
Summary of plasma concentrations by interval.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | Furosemide Plasma Concentrations | 5 hours post-dose | 2049 ng/mL | Standard Deviation 593 |
| BMS-986231 | Furosemide Plasma Concentrations | 8 hours post-dose | 426.8 ng/mL | Standard Deviation 204.8 |
| BMS-986231 | Furosemide Plasma Concentrations | 6 hours post-dose | 1122 ng/mL | Standard Deviation 437.6 |
| BMS-986231 | Furosemide Plasma Concentrations | 10 hours post-dose | 345.6 ng/mL | Standard Deviation 386.6 |
| BMS-986231 | Furosemide Plasma Concentrations | 4 hours post-dose | 1605 ng/mL | Standard Deviation 5384 |
| Placebo | Furosemide Plasma Concentrations | 10 hours post-dose | 244.3 ng/mL | Standard Deviation 164.3 |
| Placebo | Furosemide Plasma Concentrations | 4 hours post-dose | 63.6 ng/mL | Standard Deviation 140.3 |
| Placebo | Furosemide Plasma Concentrations | 5 hours post-dose | 2145 ng/mL | Standard Deviation 653.2 |
| Placebo | Furosemide Plasma Concentrations | 6 hours post-dose | 1146 ng/mL | Standard Deviation 466.8 |
| Placebo | Furosemide Plasma Concentrations | 8 hours post-dose | 476.6 ng/mL | Standard Deviation 226 |
Secondary
Furosemide Urinary Concentrations
Summary of urine recovery by interval, measured by amount excreted.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986231 | Furosemide Urinary Concentrations | Before start of infusion | 0.2 mg | Standard Deviation 0.13 |
| BMS-986231 | Furosemide Urinary Concentrations | 0-2 hours | 0.1 mg | Standard Deviation 0.08 |
| BMS-986231 | Furosemide Urinary Concentrations | 2-4 hours | 0.3 mg | Standard Deviation 0.37 |
| BMS-986231 | Furosemide Urinary Concentrations | 4-5 hours | 7.9 mg | Standard Deviation 4.66 |
| BMS-986231 | Furosemide Urinary Concentrations | 5-6 hours | 4.3 mg | Standard Deviation 1.74 |
| BMS-986231 | Furosemide Urinary Concentrations | 6-7 hours | 2.8 mg | Standard Deviation 2.03 |
| BMS-986231 | Furosemide Urinary Concentrations | 7-8 hours | 2.0 mg | Standard Deviation 1.22 |
| BMS-986231 | Furosemide Urinary Concentrations | 8-10 hours | 1.7 mg | Standard Deviation 1.28 |
| Placebo | Furosemide Urinary Concentrations | 8-10 hours | 1.6 mg | Standard Deviation 1 |
| Placebo | Furosemide Urinary Concentrations | Before start of infusion | 0.2 mg | Standard Deviation 0.11 |
| Placebo | Furosemide Urinary Concentrations | 5-6 hours | 3.7 mg | Standard Deviation 1.48 |
| Placebo | Furosemide Urinary Concentrations | 0-2 hours | 0.1 mg | Standard Deviation 0.11 |
| Placebo | Furosemide Urinary Concentrations | 7-8 hours | 1.7 mg | Standard Deviation 1.15 |
| Placebo | Furosemide Urinary Concentrations | 2-4 hours | 0.1 mg | Standard Deviation 0.11 |
| Placebo | Furosemide Urinary Concentrations | 6-7 hours | 2.7 mg | Standard Deviation 1.43 |
| Placebo | Furosemide Urinary Concentrations | 4-5 hours | 8.2 mg | Standard Deviation 4.56 |
Secondary
Number of Participants With an Abnormal Clinical Laboratory Value
Number of participants who experienced an in-study abnormal clinical laboratory event under the category of Hematology, Chemistry or Urinalysis.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986231 | Number of Participants With an Abnormal Clinical Laboratory Value | 0 Number of participants |
| Placebo | Number of Participants With an Abnormal Clinical Laboratory Value | 0 Number of participants |
Secondary
Number of Participants With an Adverse Event (AE)
Clinically relevant hypotension is defined as systolic blood pressure (SBP) \< 90 mmHg or symptomatic hypotension during infusion
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986231 | Number of Participants With an Adverse Event (AE) | 8 Number of participants |
| Placebo | Number of Participants With an Adverse Event (AE) | 6 Number of participants |
Secondary
Number of Participants With Clinically Relevant Hypotension
Clinically relevant hypotension is defined as systolic blood pressure (SBP) \< 90 mmHg or symptomatic hypotension during infusion
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986231 | Number of Participants With Clinically Relevant Hypotension | 4 Number of participants |
| Placebo | Number of Participants With Clinically Relevant Hypotension | 0 Number of participants |
Secondary
Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion
Summary of urinary concentrations 0-4 hours after furosemide Ratio = Cumulative Sodium Excretion / Cumulative Furosemide in Urine
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS-986231 | 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 |
| Placebo | Ratio Urinary Sodium (Na) to Urinary Furosemide at 8 Hours Post-start Infusion | 10.1 Ratio of Urinary Na:Urinary furosemide | Standard Deviation 4.74 |
Secondary
Telemetry
Telemetry data not collected.
Time frame: Day 1, 8 hours post-dose
Population: Analysis population is 0, data not collected