| 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 | 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. | Posted | | Mean | Standard Deviation | mL | | 4 hours | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
| | | Title | Denominators | Categories |
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| Sequence 1 | - ParticipantsOG00011
- ParticipantsOG00111
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| | t-test, 2 sided | | 0.0021 | | Mean Difference (Net) | -448 | | | 2-Sided | 95 | -714 | -183 | | | | | Superiority | | | | | t-test, 2 sided | |
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| 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 | 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. | Posted | | Mean | Standard Deviation | percent of filtered sodium | | Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| 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 | 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. | Posted | | Mean | Standard Deviation | percent of filtered potassium | | Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Furosemide Urinary Concentrations | Summary of urine recovery by interval, measured by amount excreted. | 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. | Posted | | Mean | Standard Deviation | mg | | Day 1, predose, 0-2 hours, 2-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours, 8-10 hours | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Furosemide Plasma Concentrations | Summary of plasma concentrations by interval. | 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. | Posted | | Mean | Standard Deviation | ng/mL | | Day 1: 4, 5, 6, 8, 10 hours | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| 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 | 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. | Posted | | Mean | Standard Deviation | Ratio of Urinary Na:Urinary furosemide | | 0-4 hours after furosemide | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| 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 | 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. | Posted | | Number | | Number of participants | | up to 8 hours | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| 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 | 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. | Posted | | Number | | Number of participants | | up to 8 days | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| 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. | 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. | Posted | | Number | | Number of participants | | from first dose to 30 days post-last dose (ca. 5-8 weeks) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Change From Baseline in Vital Signs - Blood Pressure | The change in baseline for vital signs was reported for each arm. | 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. | Posted | | Mean | Standard Deviation | mmHg | | Day 1, 8 hours post-dose (end of infusion) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Change From Baseline in Vital Signs - Heart Rate | The change in baseline for vital signs was reported for each arm. | 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. | Posted | | Mean | Standard Deviation | beats/min | | Day 1, 8 hours post-dose (end of infusion) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Change From Baseline in Vital Signs - Oxygen Saturation | The change in baseline for vital signs was reported for each arm. | 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. | Posted | | Mean | Standard Deviation | oxygen saturation percentage | | Day 1, 8 hours post-dose (end of infusion) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Change From Baseline in Electrocardiograms (ECGs) - Mean Heart Rate | The change in baseline for ECGs was reported for each arm. | 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. | Posted | | Mean | Standard Deviation | beats/min | | Day 1, 8 hours post-dose (end of infusion) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Change From Baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals | The change in baseline for ECGs was reported for each arm. | 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. | Posted | | Mean | Standard Deviation | msec | | Day 1, 8 hours post-dose (end of infusion) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Telemetry | Telemetry data not collected. | Analysis population is 0, data not collected | Posted | | | | | | Day 1, 8 hours post-dose | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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| Secondary | Change From Baseline in Physical Examination - Body Weight | The change in baseline for physical examinations was reported for each arm. | 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. | Posted | | Mean | Standard Deviation | kg | | Day 1, 8 hours post-dose (end of infusion) | | | | ID | Title | Description |
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| OG000 | BMS-986231 | 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. | | OG001 | Placebo | 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. |
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