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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN5381, an NPR1 Agonist, in Heart Failure Patients with Elevated Pulmonary Capillary Wedge Pressure

    Summary
    EudraCT number
    		 2021-006337-19
    Trial protocol
    		 BE   HU  
    Global end of trial date
    02 Jun 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Jun 2026
    First version publication date
    18 Jun 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    R5381-HF-2159
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05353166
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Road, Tarrytown, NY, United States, 10591
    Public contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.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
    22 Jul 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jun 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate the safety and tolerability of single doses of REGN5381 in patients with heart failure with evidence of congestion.
    Protection of trial subjects
    It is the responsibility of both the sponsor and the investigator(s) to ensure that this clinical study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the ICH guidelines for GCP and applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Jun 2022
    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
    Moldova, Republic of: 59
    Worldwide total number of subjects
    59
    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)
    34
    From 65 to 84 years
    25
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 101 participants were screened. A total of 59 participants were randomized and received study 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, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group A: Placebo
    Arm description
    		 Participants with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan received a single intravenous (IV) infusion of matching placebo for REGN5381.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 matching placebo as a single dose administered via intravenous (IV) infusion.

    Arm title
    		 Group A: REGN5381 10 mg
    Arm description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 10 milligrams (mg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Arm title
    		 Group A: REGN5381 30 mg
    Arm description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 30 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Arm title
    		 Group A: REGN5381 100 mg
    Arm description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 100 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Arm title
    		 Group A: REGN5381 300 mg
    Arm description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 300 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Arm title
    		 Group C: Placebo
    Arm description
    		 Participants with heart failure with preserved ejection fraction (HFpEF) not taking sacubitril/valsartan received a single IV infusion of matching placebo for REGN5381.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 matching placebo as a single dose administered via IV infusion.

    Arm title
    		 Group C: REGN5381 30 mg
    Arm description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 30 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Arm title
    		 Group C: REGN5381 100 mg
    Arm description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 100 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Arm title
    		 Group C: REGN5381 300 mg
    Arm description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 300 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    REGN5381
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received REGN5381 as a single dose administered via IV infusion.

    Number of subjects in period 1
    		Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Started
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Received study treatment
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Completed
    7
    3
    3
    6
    3
    18
    3
    3
    12
    Not completed
    0
    0
    0
    0
    1
    0
    0
    0
    0
         Adverse event, non-fatal
    -
    -
    -
    -
    1
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group A: Placebo
    Reporting group description
    		 Participants with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan received a single intravenous (IV) infusion of matching placebo for REGN5381.

    Reporting group title
    Group A: REGN5381 10 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 10 milligrams (mg).

    Reporting group title
    Group A: REGN5381 30 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 30 mg.

    Reporting group title
    Group A: REGN5381 100 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 100 mg.

    Reporting group title
    Group A: REGN5381 300 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 300 mg.

    Reporting group title
    Group C: Placebo
    Reporting group description
    		 Participants with heart failure with preserved ejection fraction (HFpEF) not taking sacubitril/valsartan received a single IV infusion of matching placebo for REGN5381.

    Reporting group title
    Group C: REGN5381 30 mg
    Reporting group description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 30 mg.

    Reporting group title
    Group C: REGN5381 100 mg
    Reporting group description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 100 mg.

    Reporting group title
    Group C: REGN5381 300 mg
    Reporting group description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 300 mg.

    Reporting group values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg Total
    Number of subjects
    		 7 3 3 6 4 18 3 3 12 59
    Age Categorical
    Age Group at screening
    Units: participants
        < 18 years
    		 0 0 0 0 0 0 0 0 0 0
        ≥ 18 to < 45 years
    		 0 0 0 2 0 0 0 0 0 2
        ≥ 45 to < 65 years
    		 5 3 3 3 4 7 0 2 5 32
        ≥ 65 to < 75 years
    		 2 0 0 1 0 11 3 1 6 24
        ≥ 75 years
    		 0 0 0 0 0 0 0 0 1 1
    Sex: Female, Male
    Units: participants
        Female
    		 1 0 1 1 1 5 0 0 4 13
        Male
    		 6 3 2 5 3 13 3 3 8 46
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 0 0 0 0 0 0
        Not Hispanic or Latino
    		 7 3 3 6 4 18 3 3 12 59
        Unknown or Not Reported
    		 0 0 0 0 0 0 0 0 0 0
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0 0
        Asian
    		 0 0 0 0 0 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0 0 0 0 0
        White
    		 7 3 3 6 4 18 3 3 12 59
        Unknown or Not Reported
    		 0 0 0 0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Group A: Placebo
    Reporting group description
    		 Participants with heart failure with reduced ejection fraction (HFrEF) not taking sacubitril/valsartan received a single intravenous (IV) infusion of matching placebo for REGN5381.

    Reporting group title
    Group A: REGN5381 10 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 10 milligrams (mg).

    Reporting group title
    Group A: REGN5381 30 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 30 mg.

    Reporting group title
    Group A: REGN5381 100 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 100 mg.

    Reporting group title
    Group A: REGN5381 300 mg
    Reporting group description
    		 Participants with HFrEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 300 mg.

    Reporting group title
    Group C: Placebo
    Reporting group description
    		 Participants with heart failure with preserved ejection fraction (HFpEF) not taking sacubitril/valsartan received a single IV infusion of matching placebo for REGN5381.

    Reporting group title
    Group C: REGN5381 30 mg
    Reporting group description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 30 mg.

    Reporting group title
    Group C: REGN5381 100 mg
    Reporting group description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 100 mg.

    Reporting group title
    Group C: REGN5381 300 mg
    Reporting group description
    		 Participants with HFpEF not taking sacubitril/valsartan received a single IV infusion of REGN5381 at a dose of 300 mg.

    Subject analysis set title
    Groups A and B: Placebo
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants with HFrEF or HFpEF not taking sacubitril/valsartan received a single IV infusion of matching placebo for REGN5381.

    Primary: Number of Participants with Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants with Treatment-emergent Adverse Events (TEAEs) [1]
    End point description
    An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as those adverse events with either initial onset after study drug dose or that represented an exacerbation of a pre-existing condition after the study drug dose. The safety analysis set (SAF) included all randomized participants who received any study drug.
    End point type
    Primary
    End point timeframe
    From first dose (Day 1) up to end of study (Day 126)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis not conducted.
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: participants
    1
    1
    1
    1
    3
    3
    1
    2
    4
    No statistical analyses for this end point

    Secondary: Change from Baseline in Pulmonary Capillary Wedge Pressure (PCWP)

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    End point title
    		 Change from Baseline in Pulmonary Capillary Wedge Pressure (PCWP)
    End point description
    PCWP was collected during the right heart catheterization on Day 1. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion)
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        2 hours post end of infusion n=6,3,3,4,4,18,3,3,11
    -4.7 ( 3.34 )
    -5.9 ( 6.00 )
    -4.6 ( 1.67 )
    -7.1 ( 3.12 )
    -5.8 ( 3.80 )
    -2.7 ( 1.66 )
    -5.9 ( 5.67 )
    -7.6 ( 1.50 )
    -4.8 ( 1.51 )
        4 hours post end of infusion n=6,3,3,4,4,18,3,3,11
    -5.4 ( 2.49 )
    -4.7 ( 6.24 )
    -4.7 ( 2.91 )
    -6.3 ( 2.09 )
    -7.4 ( 4.56 )
    -3.2 ( 1.95 )
    -5.8 ( 4.88 )
    -7.0 ( 0.88 )
    -5.4 ( 2.14 )
        6 hours post end of infusion n=6,3,3,4,4,18,3,2,11
    -3.8 ( 2.67 )
    -4.6 ( 5.48 )
    -3.3 ( 3.93 )
    -8.0 ( 1.59 )
    -6.7 ( 6.65 )
    -3.3 ( 2.32 )
    -4.8 ( 4.17 )
    -9.3 ( 1.41 )
    -7.2 ( 2.22 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Central Venous Pressure (CVP)

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    End point title
    		 Change from Baseline in Central Venous Pressure (CVP)
    End point description
    CVP was collected during the right heart catheterization on day 1. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (0-1 hour, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, 5-6 hours, and 6-7 hours post start of infusion)
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: mmHg
    arithmetic mean (standard deviation)
        0-1hr post start of infusion n=4,0,3,4,4,18,3,3,11
    1.7 ( 1.62 )
    99999 ( 99999 )
    -4.6 ( 7.71 )
    -0.2 ( 0.43 )
    -0.3 ( 0.44 )
    -0.3 ( 1.56 )
    -0.3 ( 1.82 )
    -0.2 ( 0.15 )
    -0.6 ( 2.52 )
        1-2hrs post start infusion n=4,0,3,4,4,18,3,3,11
    1.2 ( 2.07 )
    99999 ( 99999 )
    -4.1 ( 7.96 )
    0.0 ( 1.08 )
    -1.6 ( 1.09 )
    -0.9 ( 2.04 )
    -1.1 ( 2.58 )
    -1.7 ( 1.18 )
    -1.6 ( 2.64 )
        2-3hrs post start infusion n=4,0,3,4,4,18,3,3,11
    -0.7 ( 3.73 )
    99999 ( 99999 )
    -6.0 ( 8.37 )
    -0.3 ( 3.26 )
    -2.9 ( 1.97 )
    -1.8 ( 1.44 )
    -1.3 ( 1.41 )
    -2.1 ( 1.15 )
    -1.7 ( 2.35 )
        3-4hrs post start infusion n=4,0,3,4,4,18,3,3,11
    -0.3 ( 2.76 )
    99999 ( 99999 )
    -5.5 ( 7.95 )
    -1.3 ( 1.03 )
    -2.8 ( 1.98 )
    -1.4 ( 2.78 )
    -3.2 ( 2.15 )
    -2.3 ( 2.13 )
    -3.3 ( 2.79 )
        4-5hrs post start infusion n=4,0,3,4,4,18,3,3,11
    -0.5 ( 3.39 )
    99999 ( 99999 )
    -6.7 ( 8.67 )
    -1.5 ( 1.40 )
    -4.1 ( 3.26 )
    -2.2 ( 2.54 )
    -4.1 ( 2.80 )
    -2.9 ( 1.84 )
    -4.3 ( 2.29 )
        5-6hrs post start infusion n=4,0,3,4,4,18,3,3,11
    -0.7 ( 1.95 )
    99999 ( 99999 )
    -5.7 ( 8.61 )
    -2.3 ( 1.57 )
    -4.7 ( 3.80 )
    -2.7 ( 2.73 )
    -3.5 ( 1.24 )
    -3.6 ( 1.52 )
    -4.4 ( 2.39 )
        6-7hrs post start infusion n=4,0,3,4,4,18,3,2,11
    0.2 ( 2.23 )
    99999 ( 99999 )
    -5.6 ( 8.92 )
    -3.2 ( 2.42 )
    -4.6 ( 3.07 )
    -3.0 ( 2.48 )
    -4.1 ( 2.32 )
    -3.3 ( 0.55 )
    -5.0 ( 2.82 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Invasive Cardiac Output (CO)

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    End point title
    		 Change from Baseline in Invasive Cardiac Output (CO)
    End point description
    CO was collected during the right heart catheterization on day 1. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (0-1 hour, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, 5-6 hours, and 6-7 hours post start of infusion)
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: Liters per minute (L/min)
    arithmetic mean (standard deviation)
        0-1hr post start of infusion n=5,0,3,4,4,18,3,3,11
    0.16 ( 0.953 )
    99999 ( 99999 )
    -0.44 ( 1.258 )
    0.17 ( 0.674 )
    0.27 ( 0.157 )
    -0.14 ( 0.547 )
    -0.01 ( 0.394 )
    0.12 ( 0.260 )
    -0.36 ( 0.598 )
        1-2hrs post start infusion n=5,0,3,4,4,18,3,3,11
    0.29 ( 0.811 )
    99999 ( 99999 )
    -0.57 ( 1.555 )
    0.03 ( 0.942 )
    0.48 ( 0.829 )
    0.05 ( 0.622 )
    0.02 ( 0.552 )
    0.26 ( 0.255 )
    -0.37 ( 0.658 )
        2-3hrs post start infusion n=5,0,3,4,4,18,3,3,11
    0.00 ( 1.005 )
    99999 ( 99999 )
    -0.64 ( 1.337 )
    -0.08 ( 0.894 )
    0.31 ( 0.866 )
    0.25 ( 0.404 )
    0.39 ( 0.713 )
    0.09 ( 0.381 )
    -0.23 ( 0.849 )
        3-4hrs post start infusion n=5,0,3,4,4,18,3,3,11
    0.39 ( 0.705 )
    99999 ( 99999 )
    -0.91 ( 1.409 )
    -0.53 ( 0.946 )
    0.36 ( 1.111 )
    0.46 ( 0.807 )
    0.84 ( 0.846 )
    0.21 ( 0.386 )
    -0.08 ( 1.020 )
        4-5hrs post start infusion n=5,0,3,4,4,18,3,3,11
    0.61 ( 1.120 )
    99999 ( 99999 )
    -1.31 ( 0.444 )
    -0.12 ( 1.214 )
    0.48 ( 1.271 )
    0.75 ( 0.856 )
    0.00 ( 1.257 )
    0.12 ( 0.482 )
    -0.39 ( 1.055 )
        5-6hrs post start infusion n=5,0,3,4,4,18,3,3,11
    0.18 ( 1.128 )
    99999 ( 99999 )
    -1.06 ( 0.912 )
    0.27 ( 1.550 )
    0.18 ( 0.926 )
    0.55 ( 0.663 )
    -0.40 ( 0.993 )
    0.01 ( 0.339 )
    -0.31 ( 0.970 )
        6-7hrs post start infusion n=5,0,3,4,4,18,3,2,11
    0.06 ( 1.186 )
    99999 ( 99999 )
    -1.22 ( 0.530 )
    0.06 ( 1.140 )
    -0.01 ( 1.182 )
    0.42 ( 0.788 )
    0.14 ( 0.914 )
    -0.45 ( 0.575 )
    -0.63 ( 1.173 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Systemic Vascular Resistance (SVR)

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    End point title
    		 Change from Baseline in Systemic Vascular Resistance (SVR)
    End point description
    SVR was derived as follows: [(Mean Arterial Pressure-Central Venous Pressure)*80]/ Invasive Cardiac Output. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (0 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, and 6 hours post end of infusion)
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: dynes*second/centimeter^5 (dynes*s/cm^5)
    arithmetic mean (standard deviation)
        0 hrs post end of infusion n=1,0,0,0,4,18,3,3,11
    -532.3 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -140.4 ( 376.06 )
    -47.0 ( 249.47 )
    8.8 ( 341.15 )
    -134.2 ( 37.16 )
    110.1 ( 350.02 )
        1 hr post end of infusion n=2,0,0,0,4,18,3,3,11
    -177.8 ( 57.33 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -135.8 ( 621.85 )
    22.8 ( 281.92 )
    -111.9 ( 349.44 )
    -98.8 ( 42.21 )
    195.3 ( 316.23 )
        2 hrs post end of infusion n=4,0,3,4,4,18,3,3,11
    -200.2 ( 393.80 )
    99999 ( 99999 )
    144.4 ( 410.20 )
    -111.1 ( 161.60 )
    72.2 ( 530.78 )
    -48.4 ( 248.87 )
    -417.6 ( 436.76 )
    -87.6 ( 130.03 )
    -31.1 ( 266.34 )
        3 hrs post end of infusion n=1,0,0,0,4,18,3,3,11
    -783.1 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -8.1 ( 369.55 )
    -187.5 ( 320.75 )
    -279.4 ( 584.68 )
    -176.0 ( 157.69 )
    22.2 ( 380.63 )
        4 hrs post end of infusion n=4,0,3,4,4,18,3,3,11
    -286.9 ( 426.15 )
    99999 ( 99999 )
    337.1 ( 212.36 )
    -92.5 ( 343.89 )
    67.0 ( 499.98 )
    -204.9 ( 303.79 )
    315.9 ( 432.37 )
    -175.3 ( 233.77 )
    166.1 ( 348.38 )
        5 hrs post end of infusion n=1,0,0,0,4,18,3,2, 11
    -931.1 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    56.9 ( 199.05 )
    -74.1 ( 263.81 )
    -44.3 ( 323.25 )
    -89.4 ( 270.01 )
    103.2 ( 316.66 )
        6 hrs post end of infusion n=4,0,3,4,4,15,3,2,7
    -26.1 ( 514.13 )
    99999 ( 99999 )
    207.5 ( 35.47 )
    -273.2 ( 399.00 )
    243.2 ( 583.73 )
    -58.5 ( 262.84 )
    -53.2 ( 211.54 )
    -26.3 ( 234.13 )
    196.8 ( 369.07 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Mean Pulmonary Artery Pressure (mPAP)

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    End point title
    		 Change from Baseline in Mean Pulmonary Artery Pressure (mPAP)
    End point description
    mPAP was collected during the right heart catheterization on day 1. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (0-1 hour, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, 5-6 hours, and 6-7 hours post start of infusion)
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: mmHg
    arithmetic mean (standard deviation)
        0-1hr post start of infusion n=6,3,3,4,4,18,3,3,11
    0.5 ( 1.39 )
    -0.3 ( 5.15 )
    0.3 ( 0.84 )
    -2.2 ( 2.52 )
    -0.2 ( 1.52 )
    0.2 ( 1.46 )
    -1.4 ( 2.78 )
    -0.8 ( 0.04 )
    -0.8 ( 1.50 )
        1-2hr post start of infusion n=6,3,3,4,4,18,3,3,11
    1.1 ( 2.05 )
    4.2 ( 0.92 )
    0.6 ( 1.70 )
    -2.1 ( 2.09 )
    -1.7 ( 2.48 )
    0.2 ( 2.05 )
    -1.9 ( 2.13 )
    -2.9 ( 2.04 )
    -1.0 ( 1.89 )
        2-3hr post start of infusion n=6,3,3,4,4,18,3,3,11
    -1.6 ( 1.62 )
    0.4 ( 4.16 )
    -4.0 ( 4.61 )
    -2.3 ( 1.76 )
    -2.3 ( 1.57 )
    -0.4 ( 1.61 )
    -2.1 ( 3.94 )
    -3.6 ( 3.17 )
    -1.8 ( 2.08 )
        3-4hr post start of infusion n=6,3,3,4,4,18,3,3,11
    -1.4 ( 0.90 )
    -4.1 ( 1.27 )
    -1.4 ( 1.82 )
    -4.5 ( 1.58 )
    -2.9 ( 1.49 )
    -0.2 ( 2.56 )
    -4.3 ( 5.98 )
    -5.8 ( 4.69 )
    -2.9 ( 2.95 )
        4-5hr post start of infusion n=6,3,3,4,4,18,3,3,11
    -1.6 ( 2.40 )
    -2.1 ( 3.05 )
    -7.2 ( 9.51 )
    -2.4 ( 4.13 )
    -3.9 ( 3.89 )
    -1.6 ( 1.56 )
    -6.0 ( 5.73 )
    -6.4 ( 3.42 )
    -4.2 ( 2.10 )
        5-6hr post start of infusion n=6,3,3,4,4,18,3,3,11
    -1.9 ( 1.55 )
    -0.8 ( 2.33 )
    -3.0 ( 4.22 )
    -5.5 ( 2.08 )
    -4.6 ( 5.69 )
    -2.3 ( 2.45 )
    -5.0 ( 4.53 )
    -7.6 ( 6.64 )
    -4.6 ( 1.80 )
        6-7hr post start of infusion n=6,3,3,4,4,18,3,2,11
    -0.4 ( 1.33 )
    -0.1 ( 2.66 )
    -4.6 ( 8.28 )
    -5.5 ( 3.15 )
    -4.5 ( 4.40 )
    -2.2 ( 2.38 )
    -5.7 ( 6.79 )
    -3.8 ( 1.45 )
    -5.2 ( 2.95 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Pulmonary Vascular Resistance (PVR)

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    End point title
    		 Change from Baseline in Pulmonary Vascular Resistance (PVR)
    End point description
    Pulmonary Vascular Resistance was derived as follows: [(Mean Pulmonary Artery Pressure-Pulmonary Capillary Wedge Pressure)*80]/ Invasive Cardiac Output. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion)
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: dynes*s/cm^5
    arithmetic mean (standard deviation)
        2 hrs post end of infusion n=5,0,3,3,4,18,3,3,11
    11.5 ( 45.44 )
    99999 ( 99999 )
    72.1 ( 55.44 )
    78.2 ( 37.28 )
    89.9 ( 96.89 )
    31.5 ( 52.14 )
    13.5 ( 13.55 )
    30.0 ( 68.26 )
    59.1 ( 82.64 )
        4 hrs post end of infusion n=5,0,3,4,4,18,3,3,11
    15.3 ( 74.84 )
    99999 ( 99999 )
    84.8 ( 53.05 )
    64.1 ( 74.11 )
    114.4 ( 172.35 )
    -2.1 ( 49.65 )
    69.1 ( 42.29 )
    7.5 ( 66.87 )
    37.6 ( 46.72 )
        6 hrs post end of infusion n=5,0,3,4,4,18,3,2,11
    7.7 ( 95.34 )
    99999 ( 99999 )
    37.7 ( 38.82 )
    55.2 ( 70.42 )
    147.8 ( 164.45 )
    -1.1 ( 51.76 )
    -21.4 ( 73.65 )
    51.2 ( 35.76 )
    68.6 ( 76.60 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Systolic Blood Pressure (SBP)

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    End point title
    		 Change from Baseline in Systolic Blood Pressure (SBP)
    End point description
    The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (0, 1, 2, 3, 4, 5, 6, 7, 8 hours post end of infusion [EOI]), Day 2 to Day 5 every 8 hours, Day 6 first 8 hours, Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: mmHg
    arithmetic mean (standard deviation)
        Day 1 (0 hrs post EOI) n=3,0,0,2,4,18,3,3,12
    3.7 ( 11.59 )
    99999 ( 99999 )
    99999 ( 99999 )
    2.0 ( 8.49 )
    1.5 ( 5.57 )
    -0.8 ( 8.83 )
    1.7 ( 13.61 )
    -1.7 ( 4.51 )
    1.6 ( 9.22 )
        Day 1 (1 hr post EOI) n=3,0,0,2,4,18,3,3,12
    4.0 ( 5.29 )
    99999 ( 99999 )
    99999 ( 99999 )
    3.0 ( 1.41 )
    3.8 ( 9.00 )
    -0.5 ( 10.89 )
    -1.7 ( 13.65 )
    -4.3 ( 5.77 )
    -0.6 ( 12.70 )
        Day 1 (2 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    3.0 ( 11.02 )
    -10.3 ( 12.01 )
    -7.7 ( 5.51 )
    -7.5 ( 5.32 )
    1.3 ( 8.50 )
    -0.6 ( 10.31 )
    -13.0 ( 11.79 )
    -5.0 ( 6.56 )
    -6.7 ( 14.00 )
        Day 1 (3 hrs post EOI) n=3,0,0,2,4,18,3,3,12
    -5.0 ( 3.46 )
    99999 ( 99999 )
    99999 ( 99999 )
    -5.5 ( 6.36 )
    2.5 ( 8.50 )
    -4.7 ( 8.92 )
    -12.7 ( 10.50 )
    -12.7 ( 4.16 )
    -8.3 ( 16.09 )
        Day 1 (4 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -2.3 ( 4.03 )
    -9.0 ( 9.64 )
    -9.0 ( 13.45 )
    -2.3 ( 7.66 )
    -0.5 ( 8.35 )
    -4.6 ( 10.59 )
    2.7 ( 2.31 )
    -10.3 ( 9.24 )
    -7.5 ( 13.91 )
        Day 1 (5 hrs post EOI) n=3,0,0,2,4,18,3,3,12
    3.0 ( 12.17 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.0 ( 8.49 )
    -6.5 ( 16.42 )
    -1.9 ( 10.75 )
    -7.7 ( 15.01 )
    -6.3 ( 14.05 )
    -7.7 ( 13.98 )
        Day 1 (6 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -1.3 ( 2.56 )
    -7.3 ( 15.04 )
    -2.0 ( 6.93 )
    -5.7 ( 7.26 )
    -7.5 ( 15.61 )
    -1.5 ( 11.52 )
    -1.7 ( 10.69 )
    -5.7 ( 6.43 )
    -7.9 ( 13.21 )
        Day 2 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -6.7 ( 16.33 )
    -13.3 ( 2.08 )
    7.0 ( 20.66 )
    -7.2 ( 9.75 )
    -8.5 ( 21.19 )
    -12.9 ( 15.22 )
    -14.7 ( 15.53 )
    -8.0 ( 6.93 )
    -15.2 ( 14.55 )
        Day 2 (second 8 hrs) n=7,3,3,6,4,18,3,3,12
    -20.7 ( 15.40 )
    -17.7 ( 8.62 )
    -7.0 ( 18.33 )
    -11.0 ( 11.78 )
    -8.3 ( 25.05 )
    -21.8 ( 14.63 )
    -15.7 ( 14.05 )
    -7.3 ( 5.03 )
    -22.3 ( 8.52 )
        Day 2 (third 8 hrs) n=7,3,3,6,4,18,3,3,12
    -10.9 ( 11.81 )
    -21.7 ( 11.37 )
    -4.0 ( 24.27 )
    -9.2 ( 11.36 )
    -7.5 ( 16.84 )
    -13.4 ( 15.27 )
    -14.7 ( 9.81 )
    -14.3 ( 11.24 )
    -11.8 ( 11.09 )
        Day 3 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -16.1 ( 16.75 )
    -18.0 ( 6.24 )
    -8.7 ( 9.50 )
    -4.8 ( 10.01 )
    -7.5 ( 13.23 )
    -20.4 ( 14.21 )
    -22.3 ( 16.29 )
    -18.3 ( 11.55 )
    -11.3 ( 11.24 )
        Day 3 (second 8 hrs) n=4,0,0,3,0,18,3,3,12
    -11.0 ( 7.26 )
    99999 ( 99999 )
    99999 ( 99999 )
    -3.3 ( 9.29 )
    99999 ( 99999 )
    -15.8 ( 16.88 )
    -12.0 ( 13.23 )
    -8.7 ( 7.37 )
    -19.7 ( 13.45 )
        Day 3 (third 8 hrs) n=4,0,0,3,0,18,3,3,12
    -6.8 ( 21.25 )
    99999 ( 99999 )
    99999 ( 99999 )
    -5.3 ( 11.06 )
    99999 ( 99999 )
    -12.1 ( 15.69 )
    -6.7 ( 16.04 )
    -6.0 ( 3.46 )
    -5.6 ( 17.47 )
        Day 4 (first 8 hrs) n=4,0,0,3,1,18,3,3,12
    -7.8 ( 14.31 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.0 ( 17.58 )
    -39.0 ( 99999 )
    -18.9 ( 15.94 )
    -15.7 ( 15.57 )
    -12.3 ( 2.08 )
    -8.5 ( 13.85 )
        Day 4 (second 8 hrs) n=1,0,0,2,0,18,3,2,12
    2.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.0 ( 8.49 )
    99999 ( 99999 )
    -16.3 ( 19.67 )
    -9.3 ( 18.23 )
    -17.5 ( 2.12 )
    -9.7 ( 12.49 )
        Day 4 (third 8 hrs) n=1,0,0,2,0,18,3,2,12
    -9.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.5 ( 10.61 )
    99999 ( 99999 )
    -12.7 ( 16.84 )
    -9.3 ( 13.65 )
    -15.0 ( 5.66 )
    -9.1 ( 9.17 )
        Day 5 (first 8 hrs) n=1,0,0,2,0,18,3,3,12
    -8.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.0 ( 21.21 )
    99999 ( 99999 )
    -16.6 ( 16.98 )
    -22.3 ( 22.37 )
    -20.0 ( 13.00 )
    -10.0 ( 11.10 )
        Day 5 (second 8 hrs) n=0,0,0,1,0,2,0,0,2
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -7.0 ( 99999 )
    99999 ( 99999 )
    -6.5 ( 19.09 )
    99999 ( 99999 )
    99999 ( 99999 )
    -17.0 ( 12.73 )
        Day 5 (third 8 hrs) n=0,0,0,1,0,2,0,0,2
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.0 ( 99999 )
    99999 ( 99999 )
    -13.0 ( 18.38 )
    99999 ( 99999 )
    99999 ( 99999 )
    -5.0 ( 9.90 )
        Day 6 (first 8 hrs) n=0,0,0,1,0,0,0,0,0
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -6.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Day 8 n=7,3,3,6,3,18,3,3,12
    -4.1 ( 15.23 )
    -12.0 ( 13.75 )
    8.3 ( 4.51 )
    2.8 ( 12.73 )
    -13.3 ( 19.86 )
    -16.6 ( 17.39 )
    -21.7 ( 8.74 )
    -16.3 ( 6.43 )
    -3.9 ( 12.71 )
        Day 15 n=7,3,3,6,3,18,3,3,12
    -7.3 ( 10.48 )
    -8.7 ( 17.47 )
    9.3 ( 6.66 )
    -4.8 ( 9.99 )
    -8.0 ( 14.11 )
    -9.7 ( 15.86 )
    -15.7 ( 13.01 )
    -12.7 ( 6.81 )
    -3.8 ( 10.94 )
        Day 22 n=7,3,3,6,3,18,3,3,12
    -9.1 ( 12.08 )
    -15.7 ( 17.90 )
    4.3 ( 7.09 )
    1.3 ( 16.02 )
    0.3 ( 26.39 )
    -8.8 ( 16.37 )
    -9.0 ( 14.11 )
    -17.7 ( 10.97 )
    0.0 ( 12.95 )
        Day 36 n=6,0,3,6,3,18,3,3,12
    -14.5 ( 13.84 )
    99999 ( 99999 )
    2.3 ( 11.93 )
    1.5 ( 13.77 )
    -1.0 ( 24.76 )
    -12.4 ( 13.88 )
    -7.3 ( 13.20 )
    -11.3 ( 9.29 )
    -4.1 ( 12.84 )
        Day 57 n=5,0,0,6,3,15,0,3,12
    -4.2 ( 8.98 )
    99999 ( 99999 )
    99999 ( 99999 )
    1.8 ( 17.79 )
    -3.7 ( 25.38 )
    -10.4 ( 11.83 )
    99999 ( 99999 )
    -14.0 ( 11.53 )
    -1.4 ( 13.69 )
        Day 78 n=5,0,0,6,3,15,0,3,12
    -9.8 ( 11.90 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.5 ( 15.50 )
    -10.7 ( 17.56 )
    -9.5 ( 12.28 )
    99999 ( 99999 )
    -18.7 ( 7.64 )
    -3.5 ( 8.95 )
        Day 99 n=2,0,0,0,3,12,0,0,12
    -4.0 ( 14.14 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -13.7 ( 29.70 )
    -4.0 ( 13.21 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.3 ( 16.69 )
        Day 126 n=2,0,0,0,3,12,0,0,12
    -8.0 ( 15.56 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.7 ( 10.60 )
    -9.8 ( 16.01 )
    99999 ( 99999 )
    99999 ( 99999 )
    -6.0 ( 14.53 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Diastolic Blood Pressure (DBP)

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    End point title
    		 Change from Baseline in Diastolic Blood Pressure (DBP)
    End point description
    The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (0, 1, 2, 3, 4, 5, 6, 7, 8 hours post end of infusion [EOI]), Day 2 to Day 5 every 8 hours, Day 6 first 8 hours, Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: mmHg
    arithmetic mean (standard deviation)
        Day 1 (0 hrs post EOI) n=3,0,0,2,4,18,3,3,12
    0.3 ( 8.08 )
    99999 ( 99999 )
    9999 ( 99999 )
    6.0 ( 5.66 )
    -3.3 ( 5.62 )
    -1.0 ( 5.78 )
    0.0 ( 5.20 )
    -2.7 ( 4.51 )
    0.7 ( 6.80 )
        Day 1 (1 hr post EOI) n=3,0,0,2,4,18,3,3,12
    1.7 ( 2.89 )
    99999 ( 99999 )
    99999 ( 99999 )
    4.0 ( 2.83 )
    -1.8 ( 6.50 )
    0.8 ( 8.14 )
    -1.3 ( 2.31 )
    -4.7 ( 4.73 )
    0.8 ( 4.73 )
        Day 1 (2 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    0.9 ( 7.90 )
    -3.3 ( 6.03 )
    -7.7 ( 4.51 )
    -8.3 ( 5.28 )
    -0.5 ( 5.45 )
    -0.8 ( 7.96 )
    -9.3 ( 10.50 )
    -7.3 ( 6.66 )
    -1.2 ( 8.08 )
        Day 1 (3 hrs post EOI) n=3,0,0,2,4,18,3,3,12
    -4.7 ( 5.69 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.0 ( 8.49 )
    -1.3 ( 6.85 )
    -3.1 ( 6.77 )
    -6.3 ( 9.61 )
    -8.3 ( 1.53 )
    -3.8 ( 8.94 )
        Day 1 (4 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -3.9 ( 5.21 )
    -8.3 ( 5.77 )
    -8.0 ( 11.36 )
    -2.3 ( 6.56 )
    -3.0 ( 4.69 )
    -2.7 ( 7.69 )
    0.0 ( 4.00 )
    -7.3 ( 4.04 )
    -4.4 ( 8.20 )
        Day 1 (5 hrs post EOI) n=3,0,0,2,4,18,3,3,12
    0.0 ( 5.00 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.0 ( 4.24 )
    -4.3 ( 6.80 )
    -0.6 ( 7.24 )
    0.0 ( 8.54 )
    -5.7 ( 7.02 )
    -4.1 ( 9.17 )
        Day 1 (6 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -1.3 ( 6.32 )
    -7.7 ( 7.51 )
    -6.7 ( 13.43 )
    -4.8 ( 7.70 )
    -5.8 ( 6.50 )
    1.9 ( 9.10 )
    1.3 ( 2.89 )
    -6.7 ( 4.73 )
    -3.3 ( 8.15 )
        Day 2 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -7.3 ( 7.99 )
    -10.7 ( 1.53 )
    -0.3 ( 13.58 )
    -8.2 ( 6.82 )
    -12.8 ( 12.58 )
    -7.2 ( 9.85 )
    -9.0 ( 9.00 )
    -3.3 ( 3.21 )
    -9.1 ( 8.02 )
        Day 2 (second 8 hrs) n=7,3,3,6,4,18,3,3,12
    -15.3 ( 7.52 )
    -18.3 ( 6.35 )
    -9.0 ( 13.08 )
    -10.7 ( 7.94 )
    -13.3 ( 10.84 )
    -10.3 ( 10.03 )
    -9.7 ( 5.51 )
    -5.7 ( 7.02 )
    -13.6 ( 8.62 )
        Day 2 (third 8 hrs) n=7,3,3,6,4,18,3,3,12
    -9.7 ( 10.89 )
    -16.3 ( 7.77 )
    -9.0 ( 16.82 )
    -8.7 ( 10.27 )
    -8.5 ( 8.50 )
    -9.3 ( 9.87 )
    -11.0 ( 8.19 )
    -8.0 ( 6.24 )
    -8.2 ( 7.47 )
        Day 3 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -11.9 ( 11.98 )
    -13.7 ( 6.11 )
    -13.0 ( 8.54 )
    -8.5 ( 4.72 )
    -9.8 ( 6.24 )
    -11.3 ( 8.78 )
    -15.0 ( 15.10 )
    -8.7 ( 5.03 )
    -5.7 ( 7.40 )
        Day 3 (second 8 hrs) n=4,0,0,3,0,18,3,3,12
    -8.3 ( 6.34 )
    99999 ( 99999 )
    99999 ( 99999 )
    -5.3 ( 7.51 )
    99999 ( 99999 )
    -8.6 ( 11.12 )
    -14.3 ( 9.07 )
    -6.7 ( 4.93 )
    -10.9 ( 8.77 )
        Day 3 (third 8 hrs) n=4,0,0,3,0,18,3,3,12
    -5.3 ( 12.97 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.3 ( 11.02 )
    99999 ( 99999 )
    -7.1 ( 8.37 )
    -16.3 ( 14.22 )
    -5.3 ( 3.06 )
    -5.2 ( 11.61 )
        Day 4 (first 8 hrs) n=4,0,0,3,1,18,3,3,12
    -6.3 ( 12.53 )
    99999 ( 99999 )
    99999 ( 99999 )
    -6.3 ( 15.63 )
    -31.0 ( 99999 )
    -8.8 ( 9.01 )
    -14.7 ( 4.62 )
    -8.3 ( 4.04 )
    -6.5 ( 8.15 )
        Day 4 (second 8 hrs) n=1,0,0,2,0,18,3,2,12
    -3.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.0 ( 5.66 )
    99999 ( 99999 )
    -8.2 ( 12.28 )
    -15.3 ( 14.64 )
    -12.0 ( 8.49 )
    -6.8 ( 7.29 )
        Day 4 (third 8 hrs) n=1,0,0,2,0,18,3,2,12
    -15.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.5 ( 9.19 )
    99999 ( 99999 )
    -6.4 ( 11.54 )
    -15.7 ( 9.24 )
    -8.0 ( 5.66 )
    -7.2 ( 6.94 )
        Day 5 (first 8 hrs) n=1,0,0,2,0,18,3,3,12
    2.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.5 ( 19.09 )
    99999 ( 99999 )
    -8.1 ( 10.10 )
    -16.0 ( 15.13 )
    -11.7 ( 7.51 )
    -8.2 ( 7.93 )
        Day 5 (second 8 hrs) n=0,0,0,1,0,2,0,0,2
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -8.0 ( 99999 )
    99999 ( 99999 )
    -6.5 ( 12.02 )
    99999 ( 99999 )
    99999 ( 99999 )
    -11.5 ( 3.54 )
        Day 5 (third 8 hrs) n=0,0,0,1,0,2,0,0,2
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.0 ( 99999 )
    99999 ( 99999 )
    -9.0 ( 8.49 )
    99999 ( 99999 )
    99999 ( 99999 )
    -7.0 ( 2.83 )
        Day 6 (first 8 hrs) n=0,0,0,1,0,0,0,0,0
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -8.0 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Day 8 n=7,3,3,6,3,18,3,3,12
    -5.6 ( 13.25 )
    -7.0 ( 15.72 )
    -4.3 ( 2.89 )
    -2.7 ( 8.80 )
    -12.7 ( 13.87 )
    -9.3 ( 10.46 )
    -15.7 ( 11.93 )
    -9.3 ( 3.51 )
    -2.8 ( 7.03 )
        Day 15 n=7,3,3,6,3,18,3,3,12
    -7.7 ( 5.68 )
    -6.3 ( 13.65 )
    -1.3 ( 3.06 )
    -5.5 ( 11.15 )
    -12.7 ( 6.51 )
    -5.2 ( 8.77 )
    -10.0 ( 9.64 )
    -7.0 ( 6.00 )
    -4.8 ( 5.47 )
        Day 22 n=7,3,3,6,3,18,3,3,12
    -8.0 ( 7.26 )
    -16.3 ( 9.50 )
    -2.0 ( 5.29 )
    -2.7 ( 7.12 )
    -10.7 ( 16.62 )
    -3.1 ( 9.29 )
    -12.0 ( 9.54 )
    -9.7 ( 3.06 )
    -3.8 ( 7.59 )
        Day 36 n=6,0,3,6,3,18,3,3,12
    -12.3 ( 8.85 )
    99999 ( 99999 )
    -6.7 ( 12.42 )
    -1.5 ( 14.29 )
    -15.7 ( 20.74 )
    -5.3 ( 6.82 )
    -10.7 ( 7.37 )
    -6.7 ( 5.86 )
    -5.1 ( 12.91 )
        Day 57 n=5,0,0,6,3,15,0,3,12
    -5.8 ( 7.36 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.5 ( 15.88 )
    -17.0 ( 22.61 )
    -4.5 ( 7.02 )
    99999 ( 99999 )
    -6.3 ( 6.43 )
    -2.7 ( 5.63 )
        Day 78 n=5,0,0,6,3,15,0,3,12
    -5.6 ( 5.77 )
    99999 ( 99999 )
    99999 ( 99999 )
    -6.5 ( 14.24 )
    -16.0 ( 13.89 )
    -3.3 ( 6.69 )
    99999 ( 99999 )
    -8.3 ( 3.06 )
    -5.8 ( 6.94 )
        Day 99 n=2,0,0,0,3,12,0,0,12
    -2.0 ( 2.83 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -18.0 ( 18.25 )
    -0.3 ( 6.20 )
    99999 ( 99999 )
    99999 ( 99999 )
    -3.8 ( 8.50 )
        Day 126 n=2,0,0,0,3,12,0,0,12
    -6.0 ( 12.73 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -11.7 ( 14.01 )
    -3.8 ( 10.82 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.2 ( 10.79 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Mean Arterial Pressure (MAP)

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    End point title
    		 Change from Baseline in Mean Arterial Pressure (MAP)
    End point description
    MAP was derived as follows: (1/3*SBP + 2/3*DBP). The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion [EOI]), Day 2 (first 8 hours, second 8 hours, third 8 hours), Day 3 (first 8 hours, second 8 hours, third 8 hours), Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: mmHg
    arithmetic mean (standard deviation)
        Day 1 (2 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    1.5 ( 9.10 )
    -5.6 ( 7.13 )
    -7.3 ( 2.91 )
    -8.4 ( 5.03 )
    0.0 ( 2.33 )
    -0.5 ( 8.64 )
    -9.4 ( 11.75 )
    -7.8 ( 4.81 )
    -3.4 ( 8.69 )
        Day 1 (4 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -3.4 ( 4.30 )
    -8.8 ( 4.17 )
    -8.1 ( 12.08 )
    -2.7 ( 6.84 )
    -1.9 ( 0.96 )
    -3.3 ( 8.27 )
    2.2 ( 2.34 )
    -8.3 ( 5.70 )
    -5.4 ( 8.87 )
        Day 1 (6 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -1.0 ( 5.04 )
    -7.7 ( 11.02 )
    -5.0 ( 11.67 )
    -5.6 ( 7.96 )
    -7.2 ( 7.83 )
    0.8 ( 9.75 )
    1.6 ( 5.48 )
    -6.7 ( 4.41 )
    -5.1 ( 9.01 )
        Day 2 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -7.4 ( 10.44 )
    -12.3 ( 1.20 )
    1.9 ( 15.60 )
    -8.3 ( 6.80 )
    -11.6 ( 14.23 )
    -8.9 ( 10.93 )
    -10.2 ( 10.03 )
    -5.4 ( 3.83 )
    -11.7 ( 9.31 )
        Day 2 (second 8 hrs) n=7,3,3,6,4,18,3,3,12
    -17.0 ( 8.84 )
    -18.8 ( 7.24 )
    -8.2 ( 15.00 )
    -10.8 ( 8.72 )
    -10.8 ( 16.01 )
    -14.1 ( 9.68 )
    -11.4 ( 8.50 )
    -6.9 ( 5.83 )
    -16.8 ( 8.04 )
        Day 2 (third 8 hrs) n=7,3,3,6,4,18,3,3,12
    -10.2 ( 10.90 )
    -18.1 ( 7.43 )
    -7.7 ( 19.22 )
    -8.7 ( 10.39 )
    -7.2 ( 10.93 )
    -10.5 ( 10.10 )
    -10.3 ( 8.41 )
    -10.1 ( 7.90 )
    -9.8 ( 8.33 )
        Day 3 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -13.0 ( 12.70 )
    -15.6 ( 4.17 )
    -11.7 ( 7.62 )
    -8.1 ( 5.98 )
    9.2 ( 8.57 )
    -14.0 ( 8.91 )
    -16.9 ( 14.54 )
    -12.2 ( 6.99 )
    -7.7 ( 7.66 )
        Day 3 (second 8 hrs) n=4,0,0,3,0,18,3,3,12
    -9.6 ( 6.56 )
    99999 ( 99999 )
    99999 ( 99999 )
    -5.1 ( 6.47 )
    99999 ( 99999 )
    -10.6 ( 12.17 )
    -12.3 ( 8.19 )
    -7.6 ( 5.54 )
    -13.9 ( 9.23 )
        Day 3 (third 8hrs) n=4,0,0,3,0,18,3,3,12
    -5.6 ( 15.57 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.3 ( 10.49 )
    99999 ( 99999 )
    -8.8 ( 9.95 )
    -12.2 ( 13.49 )
    -5.8 ( 3.27 )
    -4.6 ( 13.09 )
        Day 8 n=7,3,3,6,3,18,3,3,12
    -4.3 ( 12.43 )
    -9.1 ( 14.83 )
    -0.2 ( 3.56 )
    -0.9 ( 10.06 )
    -12.9 ( 14.00 )
    -11.5 ( 12.01 )
    -16.9 ( 9.73 )
    -12.0 ( 4.26 )
    -2.4 ( 7.82 )
        Day 15 n=7,3,3,6,3,18,3,3,12
    -7.4 ( 7.15 )
    -8.0 ( 14.71 )
    1.9 ( 3.91 )
    -4.9 ( 10.56 )
    -11.2 ( 7.38 )
    -6.2 ( 10.02 )
    -12.9 ( 8.66 )
    -9.2 ( 6.74 )
    -4.2 ( 5.43 )
        Day 22 n=7,3,3,6,3,18,3,3,12
    -8.1 ( 7.78 )
    -17.3 ( 10.68 )
    0.2 ( 5.82 )
    -1.4 ( 10.23 )
    -7.0 ( 19.01 )
    -5.2 ( 10.63 )
    -8.7 ( 9.17 )
    -12.7 ( 5.46 )
    -2.9 ( 7.51 )
        Day 36 n=6,0,3,6,3,18,3,3,12
    -13.6 ( 9.41 )
    99999 ( 99999 )
    -3.6 ( 12.73 )
    -1.1 ( 12.99 )
    -11.7 ( 21.23 )
    -7.5 ( 7.78 )
    -8.6 ( 7.58 )
    -8.0 ( 7.06 )
    -5.2 ( 12.01 )
        Day 57 n=5,0,0,6,3,15,0,3,12
    -4.7 ( 3.89 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.4 ( 16.42 )
    -12.3 ( 23.69 )
    -6.5 ( 7.86 )
    99999 ( 99999 )
    -9.4 ( 7.90 )
    -2.0 ( 6.75 )
        Day 78 n=5,0,0,6,3,15,0,3,12
    -6.7 ( 6.97 )
    99999 ( 99999 )
    99999 ( 99999 )
    -3.9 ( 13.83 )
    -14.0 ( 15.77 )
    -5.7 ( 7.66 )
    99999 ( 99999 )
    -11.3 ( 2.03 )
    -5.1 ( 6.94 )
        Day 99 n=2,0,0,0,3,12,0,0,12
    -3.0 ( 2.36 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -17.1 ( 21.27 )
    -1.9 ( 7.61 )
    99999 ( 99999 )
    99999 ( 99999 )
    -3.9 ( 10.42 )
        Day 126 n=2,0,0,0,3,12,0,0,12
    -5.7 ( 4.71 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    -8.7 ( 12.00 )
    -5.9 ( 11.81 )
    99999 ( 99999 )
    99999 ( 99999 )
    -4.6 ( 11.30 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Pulse Rate (PR)

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    End point title
    		 Change from Baseline in Pulse Rate (PR)
    End point description
    The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point and "99999 " = not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion [EOI]), Day 2 (first 8 hours, second 8 hours, third 8 hours), Day 3 (first 8 hours, second 8 hours, third 8 hours), Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: beats per minute (bpm)
    arithmetic mean (standard deviation)
        Day 1 (2 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    1.3 ( 5.85 )
    -5.3 ( 7.57 )
    7.7 ( 8.33 )
    -3.5 ( 6.38 )
    11.8 ( 9.64 )
    2.4 ( 5.09 )
    8.0 ( 13.89 )
    3.7 ( 0.58 )
    6.5 ( 16.19 )
        Day 1 (4 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -5.4 ( 6.00 )
    -1.3 ( 4.93 )
    4.7 ( 2.89 )
    -0.7 ( 4.46 )
    7.5 ( 8.81 )
    2.7 ( 6.50 )
    0.0 ( 5.57 )
    4.7 ( 4.04 )
    5.0 ( 9.94 )
        Day 1 (6 hrs post EOI) n=7,3,3,6,4,18,3,3,12
    -1.7 ( 5.31 )
    -3.0 ( 8.19 )
    4.3 ( 1.15 )
    -2.0 ( 3.85 )
    16.5 ( 10.28 )
    2.9 ( 5.63 )
    9.0 ( 14.73 )
    5.3 ( 6.66 )
    4.3 ( 9.24 )
        Day 2 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    -4.4 ( 10.03 )
    -5.3 ( 11.02 )
    11.7 ( 6.66 )
    -4.5 ( 7.12 )
    17.0 ( 20.12 )
    4.2 ( 9.80 )
    1.3 ( 3.51 )
    4.7 ( 6.51 )
    1.4 ( 11.22 )
        Day 2 (second 8 hrs) n=7,3,3,6,4,18,3,3,12
    -2.3 ( 13.57 )
    -11.0 ( 1.00 )
    6.3 ( 4.93 )
    -2.2 ( 6.37 )
    6.8 ( 25.55 )
    4.1 ( 7.09 )
    -0.3 ( 3.51 )
    3.3 ( 5.51 )
    4.5 ( 8.17 )
        Day 2 (third 8 hrs) n=7,3,3,6,4,18,3,3,12
    -0.9 ( 17.33 )
    -8.3 ( 4.51 )
    4.0 ( 6.08 )
    -4.2 ( 5.56 )
    9.3 ( 22.23 )
    1.8 ( 6.39 )
    -1.3 ( 4.16 )
    1.7 ( 7.51 )
    1.3 ( 9.06 )
        Day 3 (first 8 hrs) n=7,3,3,6,4,18,3,3,12
    0.9 ( 14.65 )
    -7.0 ( 10.44 )
    1.0 ( 3.61 )
    -5.0 ( 7.32 )
    2.3 ( 18.25 )
    1.1 ( 8.05 )
    -1.3 ( 10.21 )
    2.3 ( 8.74 )
    -1.7 ( 9.61 )
        Day 3 (second 8 hrs) n=4,0,0,3,0,18,3,3,12
    10.5 ( 10.28 )
    99999 ( 99999 )
    99999 ( 99999 )
    2.0 ( 8.19 )
    99999 ( 99999 )
    1.9 ( 5.99 )
    -1.0 ( 6.24 )
    -0.3 ( 6.51 )
    0.9 ( 9.04 )
        Day 3 (third 8 hrs) n=4,0,0,3,0,18,3,3,12
    8.8 ( 6.95 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.0 ( 7.55 )
    99999 ( 99999 )
    0.2 ( 6.90 )
    -3.0 ( 4.58 )
    0.3 ( 10.69 )
    0.8 ( 6.21 )
        Day 8 n=7,3,3,6,3,18,3,3,12
    2.4 ( 10.42 )
    0.0 ( 12.77 )
    -6.0 ( 10.82 )
    -2.5 ( 5.32 )
    3.7 ( 6.43 )
    1.9 ( 8.52 )
    3.3 ( 2.52 )
    -0.3 ( 8.08 )
    4.2 ( 10.15 )
        Day 15 n=7,3,3,6,3,18,3,3,12
    -2.1 ( 16.71 )
    -1.7 ( 7.02 )
    0.7 ( 7.51 )
    -4.7 ( 8.85 )
    2.0 ( 8.89 )
    3.5 ( 7.75 )
    0.3 ( 3.51 )
    -2.3 ( 5.51 )
    1.7 ( 11.81 )
        Day 22 n=7,3,3,6,3,18,3,3,12
    0.3 ( 16.78 )
    -3.0 ( 9.64 )
    0.7 ( 8.33 )
    -4.7 ( 8.80 )
    5.0 ( 16.09 )
    4.1 ( 9.05 )
    2.0 ( 12.00 )
    -0.7 ( 11.55 )
    1.3 ( 5.68 )
        Day 36 n=6,0,3,6,3,18,3,3,12
    -3.2 ( 14.69 )
    99999 ( 99999 )
    -5.3 ( 5.13 )
    -1.3 ( 9.87 )
    7.0 ( 23.64 )
    4.7 ( 12.38 )
    6.3 ( 11.06 )
    -1.0 ( 10.58 )
    2.6 ( 13.71 )
        Day 57 n=5,0,0,6,3,15,0,3,12
    -2.0 ( 11.87 )
    99999 ( 99999 )
    99999 ( 99999 )
    2.2 ( 12.75 )
    12.0 ( 18.25 )
    2.9 ( 12.09 )
    99999 ( 99999 )
    3.3 ( 7.37 )
    4.1 ( 12.87 )
        Day 78 n=5,0,0,6,3,15,0,3,12
    -2.8 ( 10.13 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.5 ( 11.79 )
    4.7 ( 16.86 )
    4.3 ( 12.47 )
    99999 ( 99999 )
    0.7 ( 11.85 )
    4.3 ( 9.85 )
        Day 99 n=2,0,0,0,3,12,0,0,12
    4.0 ( 18.38 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    6.7 ( 20.23 )
    4.2 ( 11.40 )
    99999 ( 99999 )
    99999 ( 99999 )
    7.2 ( 10.12 )
        Day 126 n=2,0,0,0,3,12,0,0,12
    8.5 ( 17.68 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    13.3 ( 10.50 )
    5.0 ( 15.16 )
    99999 ( 99999 )
    99999 ( 99999 )
    7.3 ( 11.35 )
    No statistical analyses for this end point

    Secondary: Fold Change from Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)

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    End point title
    		 Fold Change from Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
    End point description
    NT‑proBNP is a clinical biomarker of heart failure. Coefficient of Variation for Fold Change from Baseline was computed as (standard deviation of the natural log-scale of the respective variable) *100. Fold Change from Baseline is the ratio of Post-Baseline to Baseline, and it is assumed to follow a lognormal distribution. The pharmacodynamic analysis set included all randomized participants who received any study drug and had at least 1 post-dose pharmacodynamic measurement. Here, "n" is the number of participants evaluable for this outcome measure at the specified time point, "99999 " = not applicable, and the "±" is representing the Geometric Coefficient of Variation, expressed as a percentage.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 (2 hours, 4 hours, and 6 hours post end of infusion [EOI]), Day 2 (24 hours post EOI), Day 3, Day 4, Day 5, Day 8, Day 15, Day 22, Day 36, Day 57, Day 78, Day 99, Day 126
    End point values
    		 Group A: Placebo Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: Placebo Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    7
    3
    3
    6
    4
    18
    3
    3
    12
    Units: picograms per milliliter (pg/mL)
    geometric mean (geometric coefficient of variation)
        Day 1 (2 hrs post EOI) n=7,3,3,6,4,17,3,3,12
    1.09 ( 26.9 )
    1.26 ( 30.8 )
    1.30 ( 26.9 )
    0.97 ( 14.8 )
    0.91 ( 11.2 )
    1.01 ( 12.4 )
    1.05 ( 6.6 )
    1.04 ( 18.2 )
    0.94 ( 13.2 )
        Day 1 (4 hrs post EOI) n=7,3,3,6,4,17,3,3,12
    1.13 ( 25.2 )
    1.23 ( 28.4 )
    1.36 ( 20.9 )
    0.96 ( 12.7 )
    0.95 ( 7.0 )
    0.99 ( 18.3 )
    0.97 ( 11.1 )
    1.03 ( 19.0 )
    0.89 ( 14.8 )
        Day 1 (6 hrs post EOI) n=7,3,3,6,4,17,3,3,12
    1.19 ( 28.7 )
    1.35 ( 32.6 )
    1.39 ( 20.3 )
    1.01 ( 14.4 )
    0.98 ( 10.0 )
    1.05 ( 19.8 )
    1.04 ( 12.2 )
    1.19 ( 23.7 )
    0.91 ( 20.8 )
        Day 2 (24 hrs post EOI) n=7,3,3,6,4,17,3,3,12
    1.12 ( 32.7 )
    0.96 ( 18.3 )
    1.12 ( 22.5 )
    0.64 ( 39.2 )
    1.13 ( 102.5 )
    0.99 ( 23.8 )
    0.79 ( 12.2 )
    0.74 ( 37.7 )
    0.63 ( 51.0 )
        Day 3 n=7,3,3,6,4,17,3,3,12
    0.66 ( 25.8 )
    1.00 ( 18.6 )
    1.09 ( 48.2 )
    0.75 ( 48.6 )
    1.32 ( 126.1 )
    0.77 ( 35.6 )
    0.66 ( 1.7 )
    0.69 ( 11.9 )
    0.68 ( 32.6 )
        Day 4 n=1,0,0,2,0,17,3,3,12
    0.98 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.76 ( 80.2 )
    99999 ( 99999 )
    0.80 ( 37.2 )
    0.72 ( 11.8 )
    0.71 ( 15.7 )
    0.89 ( 51.2 )
        Day 5 n=1,0,0,2,0,17,3,3,12
    0.73 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.81 ( 49.0 )
    99999 ( 99999 )
    0.72 ( 67.5 )
    0.97 ( 13.2 )
    0.89 ( 21.5 )
    0.99 ( 45.6 )
        Day 8 n=7,3,3,6,3,17,3,3,12
    1.06 ( 32.3 )
    1.45 ( 36.7 )
    3.01 ( 20.1 )
    1.57 ( 44.7 )
    1.23 ( 77.6 )
    1.11 ( 38.3 )
    1.02 ( 70.1 )
    1.53 ( 39.8 )
    1.40 ( 26.0 )
        Day 15 n=7,3,3,6,3,17,3,3,12
    0.96 ( 51.8 )
    1.41 ( 50.6 )
    2.92 ( 19.0 )
    1.07 ( 62.3 )
    1.42 ( 28.4 )
    1.18 ( 43.3 )
    2.19 ( 17.2 )
    1.47 ( 51.0 )
    1.43 ( 50.8 )
        Day 22 n=7,3,3,6,3,17,3,3,12
    1.00 ( 62.2 )
    1.20 ( 55.0 )
    1.92 ( 21.3 )
    1.17 ( 56.5 )
    0.80 ( 56.2 )
    1.30 ( 43.5 )
    1.90 ( 40.6 )
    3.34 ( 150.2 )
    1.29 ( 49.4 )
        Day 36 n=6,0,3,6,3,17,3,3,12
    0.80 ( 47.3 )
    99999 ( 99999 )
    1.41 ( 68.0 )
    0.98 ( 41.5 )
    0.59 ( 23.3 )
    1.13 ( 38.7 )
    1.41 ( 32.2 )
    2.66 ( 109.5 )
    1.24 ( 58.0 )
        Day 57 n=5,0,0,6,3,14,0,3,12
    1.04 ( 93.2 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.76 ( 58.2 )
    1.47 ( 54.3 )
    1.13 ( 36.6 )
    99999 ( 99999 )
    1.86 ( 86.3 )
    1.19 ( 48.8 )
        Day 78 n=5,0,0,6,3,14,0,3,12
    0.63 ( 56.6 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.79 ( 44.2 )
    0.46 ( 24.4 )
    1.09 ( 40.3 )
    99999 ( 99999 )
    1.75 ( 81.5 )
    0.99 ( 38.4 )
        Day 99 n=2,0,0,0,3,11,0,0,12
    0.91 ( 37.2 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.42 ( 20.5 )
    1.21 ( 42.5 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.90 ( 42.8 )
        Day 126 n=2,0,0,0,3,11,0,0,12
    0.92 ( 52.2 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.63 ( 57.0 )
    0.97 ( 37.7 )
    99999 ( 99999 )
    99999 ( 99999 )
    1.03 ( 49.5 )
    No statistical analyses for this end point

    Secondary: Peak Concentration (Cmax) of REGN5381 in Serum

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    End point title
    		 Peak Concentration (Cmax) of REGN5381 in Serum [2]
    End point description
    The pharmacokinetic analysis set (PKAS) included all participants who received any study drug and who had at least 1 non-missing result following the first dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 126
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Placebo arms not included in this endpoint.
    End point values
    		 Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    3
    3
    6
    4
    3
    3
    12
    Units: mg/L
        arithmetic mean (standard deviation)
    2.17 ( 0.208 )
    6.38 ( 1.34 )
    26.5 ( 6.06 )
    61.9 ( 14.8 )
    7.37 ( 1.29 )
    22.7 ( 4.01 )
    68.3 ( 14.1 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-time Curve from Time Zero to the Time of Last Measurable Concentration (AUClast) of REGN5381 in Serum

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    End point title
    		 Area Under the Concentration-time Curve from Time Zero to the Time of Last Measurable Concentration (AUClast) of REGN5381 in Serum [3]
    End point description
    The pharmacokinetic analysis set (PKAS) included all participants who received any study drug and who had at least 1 non-missing result following the first dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 126
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Placebo arms not included in this endpoint.
    End point values
    		 Group A: REGN5381 10 mg Group A: REGN5381 30 mg Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg
    Number of subjects analysed
    3
    3
    6
    4
    3
    3
    12
    Units: day*mg/L
        arithmetic mean (standard deviation)
    5.12 ( 0.284 )
    35.3 ( 7.99 )
    241 ( 29.2 )
    583 ( 345 )
    47.2 ( 16.6 )
    221 ( 38.5 )
    897 ( 149 )
    No statistical analyses for this end point

    Secondary: Number of Participants with Anti-drug Antibodies (ADA)

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    End point title
    		 Number of Participants with Anti-drug Antibodies (ADA) [4]
    End point description
    The ADA status of each participant was classified as one of the following: • Negative — If all samples were found to be negative in the ADA assay • Pre-existing immunoreactivity — If the baseline sample was positive and all post baseline ADA titers were reported as less than 9-fold the baseline titer value • Treatment-Boosted Response • Treatment-Emergent Response The ADA analysis set included all participants who received study drug and had at least 1 non-missing ADA result following the first study drug dose.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 126
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Placebo arms A and B combined
    End point values
    		 Group A: REGN5381 100 mg Group A: REGN5381 300 mg Group C: REGN5381 30 mg Group C: REGN5381 100 mg Group C: REGN5381 300 mg Groups A and B: Placebo
    Number of subjects analysed
    6
    3
    3
    3
    12
    22
    Units: participants
        Negative
    6
    3
    3
    3
    11
    22
        Pre-existing Immunoreactivity
    0
    0
    0
    0
    0
    0
        Treatment-Boosted Response
    0
    0
    0
    0
    0
    0
        Treatment-Emergent Response
    0
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From date of informed consent up to end of study (Day 126)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Group_A Placebo
    Reporting group description
    		 -

    Reporting group title
    Group_A R5381 - IV 10 mg
    Reporting group description
    		 -

    Reporting group title
    Group_A R5381 - IV 30 mg
    Reporting group description
    		 -

    Reporting group title
    Group_A R5381 - IV 100 mg
    Reporting group description
    		 -

    Reporting group title
    Group_A R5381 - IV 300 mg
    Reporting group description
    		 -

    Reporting group title
    Group_C Placebo
    Reporting group description
    		 -

    Reporting group title
    Group_C R5381 - IV 30 mg
    Reporting group description
    		 -

    Reporting group title
    Group_C R5381 - IV 100 mg
    Reporting group description
    		 -

    Reporting group title
    Group_C R5381 - IV 300 mg
    Reporting group description
    		 -

    Serious adverse events
    		 Group_A Placebo Group_A R5381 - IV 10 mg Group_A R5381 - IV 30 mg Group_A R5381 - IV 100 mg Group_A R5381 - IV 300 mg Group_C Placebo Group_C R5381 - IV 30 mg Group_C R5381 - IV 100 mg Group_C R5381 - IV 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Respiratory tract procedural complication
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group_A Placebo Group_A R5381 - IV 10 mg Group_A R5381 - IV 30 mg Group_A R5381 - IV 100 mg Group_A R5381 - IV 300 mg Group_C Placebo Group_C R5381 - IV 30 mg Group_C R5381 - IV 100 mg Group_C R5381 - IV 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    3 / 4 (75.00%)
    3 / 18 (16.67%)
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    4 / 12 (33.33%)
    Investigations
    Weight increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 18 (5.56%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 18 (5.56%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Ventricular extrasystoles
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Catheter site discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 18 (5.56%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    1
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    0 / 18 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 18 (5.56%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Mar 2022
    Amendment 1: The purpose of this amendment was to change references of this being a phase 1b study to phase 2a.
    30 Aug 2022
    Amendment 2: The main purpose of this amendment was to modify the protocol following feedback from various Health Authorities.
    25 Oct 2022
    Amendment 3: The main purpose of this amendment was to incorporate additional separate cohorts to include participants with left ventricular ejection fraction ≥50%, to include participants currently taking sacubitril/valsartan, and to test a dose of ≤300 mg REGN5381.
    21 Mar 2023
    Amendment 4: The purpose of this amendment was to modify the inclusion and exclusion criteria.
    31 Jul 2023
    Amendment 5: The main purpose of this amendment was to implement additional safety measures and incorporate additional study eligibility requirements to help mitigate potential risks.
    09 Feb 2024
    Amendment 6: The main purpose of this amendment was to implement changes to align with the latest EU-CTR guidelines and incorporate Health Authority recommendations.

    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
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