Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Cross-over Phase 2 Study of Continuous 8-Hour Intravenous Infusions of BMS-986231 in Patients with Heart Failure and Impaired Systolic Function Given a Standard Dose of Loop Diuretic

    Summary
    EudraCT number
    		 2018-000970-31
    Trial protocol
    		 GB  
    Global end of trial date
    09 Jan 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jan 2021
    First version publication date
    24 Jan 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CV013-034
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Feb 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jan 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate the effects of HNO donor BMS-986231 on 4-hour urine output in participants with HFrEF after administration of 40 mg of IV furosemide.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Nov 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 23
    Worldwide total number of subjects
    23
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    8
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 23 participants were randomized/assigned to treatment, and 23 initiated period 1 treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986231
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosed period 2

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosed period 1

    Arm title
    		 Sequence 2
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosed period 2

    Investigational medicinal product name
    BMS-986231
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosed period 1

    Number of subjects in period 1
    		Sequence 1 Sequence 2
    Started
    12
    11
    Period 1 (P1) completion
    12
    11
    Period 2 (P2) completion
    11 [1]
    10
    Completed
    12
    10
    Not completed
    0
    1
         Adverse event, non-fatal
    -
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 1 participant did not complete Period 2 but remained in the study, completing the study

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Sequence 1
    Reporting group description
    		 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.

    Reporting group title
    Sequence 2
    Reporting group description
    		 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.

    Reporting group values
    		 Sequence 1 Sequence 2 Total
    Number of subjects
    		 12 11 23
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 6 2 8
        >=65 years
    		 6 9 15
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 67.7 ± 8.19 69.8 ± 8.23 -
    Sex: Female, Male
    Units: Participants
        Female
    		 1 1 2
        Male
    		 11 10 21
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 1 0 1
        White
    		 11 11 22
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0
        Not Hispanic or Latino
    		 12 11 23
        Unknown or Not Reported
    		 0 0 0

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Sequence 1
    Reporting group description
    		 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.

    Reporting group title
    Sequence 2
    Reporting group description
    		 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.

    Subject analysis set title
    BMS-986231
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    BMS-986231
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    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.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    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.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    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.

    Subject analysis set title
    BMS-986231
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    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.

    Subject analysis set title
    BMS-986231
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    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.

    Primary: 4-hour urinary output following intravenous administration of 40 mg furosemide to HFrEF participants receiving BMS-986231 infusion compared to placebo

    		 Close Top of page
    End point title
    		 4-hour urinary output following intravenous administration of 40 mg furosemide to HFrEF participants receiving BMS-986231 infusion compared to placebo
    End point description
    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
    End point type
    Primary
    End point timeframe
    4 hours
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    21
    21
    Units: mL
    arithmetic mean (standard deviation)
        Sequence 1
    900.7 ± 366.56
    1603.3 ± 674.18
        Sequence 2
    1176.7 ± 386.21
    1345.4 ± 391.11
        Total
    1032.1 ± 392.74
    1480.5 ± 559.92
    Statistical analysis title
    		 Percent change of Drug vs placebo
    Comparison groups
    Placebo v BMS-986231
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.0222
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -22.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.7
         upper limit
    		 -3.51
    Notes
    [1] - Percent change Drug - placebo
    Statistical analysis title
    		 Drug vs placebo
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0021
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -448
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -714
         upper limit
    		 -183

    Secondary: FeNa in participants with HFrEF while on BMS-986231 compared to placebo

    		 Close Top of page
    End point title
    		 FeNa in participants with HFrEF while on BMS-986231 compared to placebo
    End point description
    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
    End point type
    Secondary
    End point timeframe
    Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: percent of filtered sodium
    arithmetic mean (standard deviation)
        Before start of infusion
    0.5 ± 0.52
    0.6 ± 0.73
        0-4 hours
    0.6 ± 0.67
    0.7 ± 0.84
        4-5 hours
    4.6 ± 3.34
    5.4 ± 3.09
        5-6 hours
    5.0 ± 2.87
    7.0 ± 3.51
        6-7 hours
    3.3 ± 2.33
    4.7 ± 2.79
        7-8 hours
    1.7 ± 1.26
    3.3 ± 2.52
    Statistical analysis title
    		 Drug - placebo, 0-4 hours after furosemide
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    P-value
    		 = 0.0163
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.63
         upper limit
    		 -0.876
    Notes
    [2] - Drug - placebo, 0-4 hours after furosemide
    Statistical analysis title
    		 Percent change, 0-4 hours after furosemide
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    P-value
    		 = 0.2018
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.8
         upper limit
    		 8.77
    Notes
    [3] - Percent change Drug - placebo, 0-4 hours after furosemide
    Statistical analysis title
    		 Drug - placebo, 0-8 hours after start of infusion
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    P-value
    		 = 0.0526
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.27
         upper limit
    		 0.0446
    Notes
    [4] - Drug - placebo, 0-8 hours after start of infusion
    Statistical analysis title
    		 Percent change, 0-8 hours after start of infusion
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    P-value
    		 = 0.2076
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -14.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.8
         upper limit
    		 9
    Notes
    [5] - Percent change Drug - placebo, 0-8 hours after start of infusion

    Secondary: FeK in participants with HFrEF while on BMS-986231 compared to placebo

    		 Close Top of page
    End point title
    		 FeK in participants with HFrEF while on BMS-986231 compared to placebo
    End point description
    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
    End point type
    Secondary
    End point timeframe
    Day 1, predose; 0-4 hours, 4-5 hours, 5-6 hours, 6-7 hours, 7-8 hours
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: percent of filtered potassium
    arithmetic mean (standard deviation)
        Before start of infusion
    0.4 ± 0.16
    0.4 ± 0.17
        0-4 hours
    0.5 ± 0.20
    0.4 ± 0.17
        4-5 hours
    1.1 ± 0.67
    0.9 ± 0.46
        5-6 hours
    1.2 ± 0.54
    1.2 ± 0.52
        6-7 hours
    1.1 ± 0.42
    1.0 ± 0.35
        7-8 hours
    1.0 ± 0.32
    0.8 ± 0.32
    Statistical analysis title
    		 Drug - placebo, 0-4 hours after furosemide
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [6]
    P-value
    		 = 0.1621
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.431
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.189
         upper limit
    		 1.05
    Notes
    [6] - Drug - placebo, 0-4 hours after furosemide
    Statistical analysis title
    		 Percent change, 0-4 hours after furosemide
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    P-value
    		 = 0.0338
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.72
         upper limit
    		 61.3
    Notes
    [7] - Percent change Drug - placebo, 0-4 hours after furosemide
    Statistical analysis title
    		 Drug - placebo, 0-8 hours after start of infusion
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [8]
    P-value
    		 = 0.06
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.766
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0353
         upper limit
    		 1.57
    Notes
    [8] - Drug - placebo, 0-8 hours after start of infusion
    Statistical analysis title
    		 Percent change, 0-8 hours after start of infusion
    Comparison groups
    BMS-986231 v Placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [9]
    P-value
    		 = 0.028
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    33.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.02
         upper limit
    		 63
    Notes
    [9] - Percent change Drug - placebo, 0-8 hours after start of infusion

    Secondary: Furosemide urinary concentrations

    		 Close Top of page
    End point title
    		 Furosemide urinary concentrations
    End point description
    Summary of urine recovery by interval, measured by amount excreted.
    End point type
    Secondary
    End point 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
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: mg
    arithmetic mean (standard deviation)
        Before start of infusion
    0.2 ± 0.13
    0.2 ± 0.11
        0-2 hours
    0.1 ± 0.08
    0.1 ± 0.11
        2-4 hours
    0.3 ± 0.37
    0.1 ± 0.11
        4-5 hours
    7.9 ± 4.66
    8.2 ± 4.56
        5-6 hours
    4.3 ± 1.74
    3.7 ± 1.48
        6-7 hours
    2.8 ± 2.03
    2.7 ± 1.43
        7-8 hours
    2.0 ± 1.22
    1.7 ± 1.15
        8-10 hours
    1.7 ± 1.28
    1.6 ± 1.00
    No statistical analyses for this end point

    Secondary: Furosemide plasma concentrations

    		 Close Top of page
    End point title
    		 Furosemide plasma concentrations
    End point description
    Summary of plasma concentrations by interval.
    End point type
    Secondary
    End point timeframe
    Day 1: 4, 5, 6, 8, 10 hours
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: ng/mL
    arithmetic mean (standard deviation)
        4 hours post-dose
    1605 ± 5384
    63.6 ± 140.3
        5 hours post-dose
    2049 ± 593.0
    2145 ± 653.2
        6 hours post-dose
    1122 ± 437.6
    1146 ± 466.8
        8 hours post-dose
    426.8 ± 204.8
    476.6 ± 226.0
        10 hours post-dose
    345.6 ± 386.6
    244.3 ± 164.3
    No statistical analyses for this end point

    Secondary: Ratio urinary sodium (Na) to urinary furosemide at 8 hours post-start infusion

    		 Close Top of page
    End point title
    		 Ratio urinary sodium (Na) to urinary furosemide at 8 hours post-start infusion
    End point description
    Summary of urinary concentrations 0-4 hours after furosemide Ratio = Cumulative Sodium Excretion / Cumulative Furosemide in Urine Note: 9999 represents NA (not applicable)
    End point type
    Secondary
    End point timeframe
    0-4 hours after furosemide
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    21
    21
    Units: Ratio of Urinary Na:Urinary furosemide
    arithmetic mean (standard deviation)
        Drug and placebo
    6.1 ± 3.18
    10.1 ± 4.74
        Difference between drug and placebo
    -4.0 ± 4.74
    9999 ± 9999
    No statistical analyses for this end point

    Secondary: Number of participants with clinically relevant hypotension

    		 Close Top of page
    End point title
    		 Number of participants with clinically relevant hypotension
    End point description
    Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion
    End point type
    Secondary
    End point timeframe
    up to 8 hours
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: Number of participants
    4
    0
    No statistical analyses for this end point

    Secondary: Number of participants with an Adverse Event (AE)

    		 Close Top of page
    End point title
    		 Number of participants with an Adverse Event (AE)
    End point description
    Clinically relevant hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or symptomatic hypotension during infusion
    End point type
    Secondary
    End point timeframe
    up to 8 days
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: Number of participants
    8
    6
    No statistical analyses for this end point

    Secondary: Number of participants with an Abnormal Clinical Laboratory Value

    		 Close Top of page
    End point title
    		 Number of participants with an Abnormal Clinical Laboratory Value
    End point description
    Number of participants who experienced an in-study abnormal clinical laboratory event under the category of Hematology, Chemistry or Urinalysis.
    End point type
    Secondary
    End point timeframe
    from first dose to 30 days post-last dose (ca. 5-8 weeks)
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    23
    Units: Number of participants
    0
    0
    No statistical analyses for this end point

    Secondary: Change from baseline in Vital Signs - blood pressure

    		 Close Top of page
    End point title
    		 Change from baseline in Vital Signs - blood pressure
    End point description
    The change in baseline for vital signs was reported for each arm.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose (end of infusion)
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    22
    Units: mmHg
    arithmetic mean (standard deviation)
        diastolic blood pressure
    -14.5 ± 9.99
    -0.6 ± 10.46
        systolic blood pressure
    -28.4 ± 15.60
    -4.9 ± 14.55
    No statistical analyses for this end point

    Secondary: Change from baseline in Vital Signs - heart rate

    		 Close Top of page
    End point title
    		 Change from baseline in Vital Signs - heart rate
    End point description
    The change in baseline for vital signs was reported for each arm.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose (end of infusion)
    End point values
    		 Placebo BMS-986231
    Number of subjects analysed
    22
    22
    Units: beats/min
        arithmetic mean (standard deviation)
    -0.1 ± 8.08
    0.5 ± 10.40
    No statistical analyses for this end point

    Secondary: Change from baseline in Vital Signs - oxygen saturation

    		 Close Top of page
    End point title
    		 Change from baseline in Vital Signs - oxygen saturation
    End point description
    The change in baseline for vital signs was reported for each arm.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose (end of infusion)
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    23
    22
    Units: oxygen saturation percentage
        arithmetic mean (standard deviation)
    -1.0 ± 1.82
    0.0 ± 1.56
    No statistical analyses for this end point

    Secondary: Change from baseline in Electrocardiograms (ECGs) - mean heart rate

    		 Close Top of page
    End point title
    		 Change from baseline in Electrocardiograms (ECGs) - mean heart rate
    End point description
    The change in baseline for ECGs was reported for each arm.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose (end of infusion)
    End point values
    		 Placebo BMS-986231
    Number of subjects analysed
    21
    23
    Units: beats/min
        arithmetic mean (standard deviation)
    1.6 ± 7.61
    0.9 ± 7.97
    No statistical analyses for this end point

    Secondary: Change from baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals

    		 Close Top of page
    End point title
    		 Change from baseline in Electrocardiograms (ECGs) - PR, QRS Duration, QT, QTcF Intervals
    End point description
    The change in baseline for ECGs was reported for each arm.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose (end of infusion)
    End point values
    		 Placebo BMS-986231
    Number of subjects analysed
    21
    23
    Units: msec
    arithmetic mean (standard deviation)
        PR Interval, Aggregate
    -2.8 ± 12.17
    2.0 ± 24.21
        QRS Duration, Aggregate
    2.2 ± 21.46
    -0.9 ± 25.91
        QT Interval, Aggregate
    -7.9 ± 16.95
    -9.1 ± 27.88
        QTcF Interval, Aggregate
    -5.1 ± 16.74
    -11.2 ± 26.90
    No statistical analyses for this end point

    Secondary: Telemetry

    		 Close Top of page
    End point title
    		 Telemetry
    End point description
    Telemetry data not collected.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    0 [10]
    0 [11]
    Units: Number of Participants
    Notes
    [10] - Analysis population is 0, data not collected
    [11] - Analysis population is 0, data not collected
    No statistical analyses for this end point

    Secondary: Change from baseline in Physical Examination - body weight

    		 Close Top of page
    End point title
    		 Change from baseline in Physical Examination - body weight
    End point description
    The change in baseline for physical examinations was reported for each arm.
    End point type
    Secondary
    End point timeframe
    Day 1, 8 hours post-dose (end of infusion)
    End point values
    		 BMS-986231 Placebo
    Number of subjects analysed
    20
    19
    Units: kg
        arithmetic mean (standard deviation)
    0.2 ± 0.77
    -0.5 ± 0.72
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from the time of signing the consent up to 30 days of discontinuation of dosing
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were intravenously administered with a single infusion of BMS-986231 matching placebo at a dose of 20 milliliter per hour for 8 hours.

    Reporting group title
    BMS-986231
    Reporting group description
    		 Subjects were intravenously administered with a single infusion of BMS-986231 at a dose of 12 microgram per kilogram per minute for 8 hours (20 milliliter per hour).

    Serious adverse events
    		 Placebo BMS-986231
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 23 (4.35%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo BMS-986231
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 23 (13.04%)
    6 / 23 (26.09%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 23 (0.00%)
    3 / 23 (13.04%)
         occurrences all number
    0
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    2
    Headache
         subjects affected / exposed
    1 / 23 (4.35%)
    3 / 23 (13.04%)
         occurrences all number
    1
    3
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 23 (0.00%)
         occurrences all number
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jan 2019
     Update of the address for BMS  Update of the Medical Monitor  Update of Appendix 3 to clarify the definition of adverse event to be used in the study  Correction position vital signs in Table 1 In addition, minor editorial corrections were included
    14 Mar 2019
     Allowance of more flexibility to the investigators regarding withholding diuretics and fluid intake and emphasizing that the target population should be patients with stable chronic heart failure with reduced ejection fraction (HFrEF) without signs of decompensation.  Clarification that if the end of infusion occurs prior to 8 hours after start of infusion (H8), the end of infusion should be considered an early discontinuation.  Minor editorial and administrative changes.
    15 Apr 2019
     Changes to Section 5.1 Inclusion Criteria, to allow participants with lower levels of baseline natriuretic peptides and higher baseline estimated glomerular filtration rate (eGFR).  Minor editorial or administrative changes or corrections of typographical errors.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 05:53:17 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA