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    Clinical Trial Results:
    A Phase 4 Double-Blinded, Randomized, Active Comparator-Controlled Clinical Trial to Study the Efficacy, Safety, and Pharmacokinetics of Sugammadex (MK-8616) for Reversal of Neuromuscular Blockade in Pediatric Participants

    Summary
    EudraCT number
    		 2017-000692-92
    Trial protocol
    		 AT   ES   FI   BE   DK  
    Global end of trial date
    28 Jan 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    27 Feb 2021
    First version publication date
    09 Aug 2020
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    8616-089
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03351608
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Jan 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jan 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jan 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This trial will evaluate the efficacy, safety, and pharmacokinetics of sugammadex for the reversal of both moderate and deep neuromuscular blockade (NMB) induced by either rocuronium or vecuronium in pediatric participants. The primary efficacy hypothesis of this investigation is that sugammadex is superior to neostigmine in reversing moderate NMB in pediatric participants as measured by time to recovery to a train-of-four (TOF) ratio of ≥0.9.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Feb 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 26
    Country: Number of subjects enrolled
    Belgium: 27
    Country: Number of subjects enrolled
    Denmark: 15
    Country: Number of subjects enrolled
    Finland: 24
    Country: Number of subjects enrolled
    Germany: 67
    Country: Number of subjects enrolled
    Spain: 20
    Country: Number of subjects enrolled
    Turkey: 16
    Country: Number of subjects enrolled
    United States: 93
    Worldwide total number of subjects
    288
    EEA total number of subjects
    179
    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)
    214
    Adolescents (12-17 years)
    74
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Male and female participants 2 to <17 years of age who are categorized as American Society of Anesthesiologists (ASA) Physical Class 1, 2, or 3 and had a planned medical and/or surgical procedure requiring moderate or deep NMB with ROC or VEC that would allow for neuromuscular monitoring were recruited.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part A: Sugammadex 2 mg/kg
    Arm description
    		 For moderate NMB reversal, a single intravenous (i.v.) bolus of sugammadex (2 mg/kg) was given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616 BRIDION
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) is given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Arm title
    		 Part A: Sugammadex 4 mg
    Arm description
    		 For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616 BRIDION
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) is given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).

    Arm title
    		 Part B: Sugammadex 2 mg/kg
    Arm description
    		 For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) was given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616 BRIDION
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) is given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Arm title
    		 Part B: Sugammadex 4 mg/kg
    Arm description
    		 For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616 BRIDION
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) is given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).

    Arm title
    		 Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Arm description
    		 For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as either glycopyrrolate (10 μg/kg) or atropine (20 µg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Neostigmine + Glycopyrrolate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as glycopyrrolate (10 μg/kg) will be given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Investigational medicinal product name
    Neostigmine + Atropine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as atropine (20 μg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Number of subjects in period 1
    		Part A: Sugammadex 2 mg/kg Part A: Sugammadex 4 mg Part B: Sugammadex 2 mg/kg Part B: Sugammadex 4 mg/kg Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Started
    19
    23
    35
    176
    35
    Completed
    18
    21
    32
    168
    33
    Not completed
    1
    2
    3
    8
    2
         Randomized by mistake, no treatment given
    -
    -
    -
    1
    -
         Physician decision
    1
    -
    -
    2
    1
         Other
    -
    1
    1
    3
    -
         Lost to follow-up
    -
    1
    1
    1
    1
         Withdrawal by parent/guardian
    -
    -
    1
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A: Sugammadex 2 mg/kg
    Reporting group description
    		 For moderate NMB reversal, a single intravenous (i.v.) bolus of sugammadex (2 mg/kg) was given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Reporting group title
    Part A: Sugammadex 4 mg
    Reporting group description
    		 For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).

    Reporting group title
    Part B: Sugammadex 2 mg/kg
    Reporting group description
    		 For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) was given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Reporting group title
    Part B: Sugammadex 4 mg/kg
    Reporting group description
    		 For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).

    Reporting group title
    Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Reporting group description
    		 For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as either glycopyrrolate (10 μg/kg) or atropine (20 µg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Reporting group values
    		 Part A: Sugammadex 2 mg/kg Part A: Sugammadex 4 mg Part B: Sugammadex 2 mg/kg Part B: Sugammadex 4 mg/kg Part B: Neostigmine + (Glycopyrrolate or Atropine) Total
    Number of subjects
    		 19 23 35 176 35 288
    Age Categorical
    Units: Subjects
        Children (2-11 years)
    		 15 17 25 132 25 214
        Adolescents (12-17 years)
    		 4 6 10 44 10 74
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 7.1 ± 4.7 7.2 ± 5.0 7.9 ± 4.4 7.9 ± 4.4 8.7 ± 4.4 -
    Gender Categorical
    Units: Subjects
        Female
    		 11 12 20 95 18 156
        Male
    		 8 11 15 81 17 132
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 0 0 0 1
        Asian
    		 0 2 3 5 2 12
        Black or African American
    		 1 2 1 2 0 6
        Multiple
    		 2 1 0 4 0 7
        White
    		 16 17 30 161 33 257
        Not Reported
    		 0 0 1 4 0 5

    End points

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    End points reporting groups
    Reporting group title
    Part A: Sugammadex 2 mg/kg
    Reporting group description
    		 For moderate NMB reversal, a single intravenous (i.v.) bolus of sugammadex (2 mg/kg) was given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Reporting group title
    Part A: Sugammadex 4 mg
    Reporting group description
    		 For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).

    Reporting group title
    Part B: Sugammadex 2 mg/kg
    Reporting group description
    		 For moderate NMB reversal, a single i.v. bolus of sugammadex (2 mg/kg) was given after final dose of neuromuscular blocking agent (NMBA; rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Reporting group title
    Part B: Sugammadex 4 mg/kg
    Reporting group description
    		 For deep NMB reversal, a single i.v. bolus of sugammadex (4 mg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of detection of a target of 1 to 2 post-tetanic counts and no response to TOF stimulations (TOF=0).

    Reporting group title
    Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Reporting group description
    		 For moderate NMB reversal, a single i.v. bolus containing both neostigmine (50 μg/kg; up to 5 mg maximum dose) as well as either glycopyrrolate (10 μg/kg) or atropine (20 µg/kg) was given after final dose of NMBA (rocuronium or vecuronium) and within 2 minutes of the reappearance of a second twitch (T2) in response to TOF stimulations.

    Subject analysis set title
    Part A: Sugammadex 2 mg (2 to <6 years)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants in Part A receiving sugammadex 2 mg and who are 2 to <6 years of age are included.

    Subject analysis set title
    Part A: Sugammadex 2 mg (6 to <12 years)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants in Part A receiving sugammadex 2 mg and who are 6 to <12 years of age are included.

    Subject analysis set title
    Part A: Sugammadex 2 mg (12 to <17 years)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants in Part A receiving sugammadex 2 mg and who are 12 to <17 years of age are included.

    Subject analysis set title
    Part A: Sugammadex 4 mg (2 to <6 years)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants in Part A receiving sugammadex 4 mg and who are 2 to <6 years of age are included.

    Subject analysis set title
    Part A: Sugammadex 4 mg (6 to <12 years)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants in Part A receiving sugammadex 4 mg and who are 6 to <12 years of age are included.

    Subject analysis set title
    Part A: Sugammadex 4 mg (12 to <17 years)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants in Part A receiving sugammadex 4 mg and who are 12 to <17 years of age are included.

    Subject analysis set title
    Parts A and B: Sugammadex 2 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants in Parts A and B who received sugammadex 2 mg are included in the analysis.

    Subject analysis set title
    Parts A and B: Sugammadex 4 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants in Parts A and B who received sugammadex 4 mg are included in the analysis.

    Primary: Area Under the Plasma Concentration-Time Curve (AUC) from Dosing to Infinity (AUC0-∞) of Sugammadex [Part A]

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    End point title
    		 Area Under the Plasma Concentration-Time Curve (AUC) from Dosing to Infinity (AUC0-∞) of Sugammadex [Part A] [1]
    End point description
    The AUCo-∞ for sugammadex, defined as the area under the plasma concentration versus time plot, was determined in each Part A arm. All participants with ≥5 post-dosing samples available are included.
    End point type
    Primary
    End point timeframe
    2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
    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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years)
    Number of subjects analysed
    9
    5
    4
    8
    6
    6
    Units: hr*μg/mL
        geometric mean (geometric coefficient of variation)
    14.1 ± 19.4
    18.8 ± 27.4
    27.6 ± 58.0
    26.9 ± 18.5
    38.2 ± 73.0
    49.2 ± 20.1
    No statistical analyses for this end point

    Primary: Plasma Clearance (CL) of Sugammadex [Part A]

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    End point title
    		 Plasma Clearance (CL) of Sugammadex [Part A] [2]
    End point description
    The CL of sugammadex, defined as the rate of elimination relative to plasma concentration, was determined in each Part A arm. All participants with ≥5 post-dosing samples available are included.
    End point type
    Primary
    End point timeframe
    2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
    Notes
    [2] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years)
    Number of subjects analysed
    9
    5
    4
    8
    6
    6
    Units: L/hr
        geometric mean (geometric coefficient of variation)
    2.30 ± 21.4
    3.58 ± 26.2
    4.68 ± 52.5
    2.26 ± 29.4
    3.43 ± 105
    5.69 ± 24.1
    No statistical analyses for this end point

    Primary: Apparent Volume of Distribution (Vz) of Sugammadex [Part A]

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    End point title
    		 Apparent Volume of Distribution (Vz) of Sugammadex [Part A] [3]
    End point description
    The Vz of sugammadex, defined as the amount of drug administered relative to plasma concentrations, was determined in each Part A arm. All participants with ≥5 post-dosing samples available are included.
    End point type
    Primary
    End point timeframe
    2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
    Notes
    [3] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years)
    Number of subjects analysed
    9
    5
    4
    8
    6
    6
    Units: Liters
        geometric mean (geometric coefficient of variation)
    3.58 ± 21.3
    6.65 ± 33.5
    10.8 ± 34.8
    4.00 ± 37.7
    8.22 ± 82.9
    12.3 ± 35.9
    No statistical analyses for this end point

    Primary: Maximum Plasma Concentration (Cmax) of Sugammadex [Part A]

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    End point title
    		 Maximum Plasma Concentration (Cmax) of Sugammadex [Part A] [4]
    End point description
    The Cmax of sugammadex, defined as the maximum plasma concentration, was determined in each Part A arm. All participants with ≥5 post-dosing samples available are included.
    End point type
    Primary
    End point timeframe
    2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
    Notes
    [4] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years)
    Number of subjects analysed
    9
    5
    4
    8
    6
    6
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    17.5 ± 33.1
    32.2 ± 15.6
    41.3 ± 85.8
    47.1 ± 22.1
    51.6 ± 69.2
    61.9 ± 13.5
    No statistical analyses for this end point

    Primary: Plasma Half-Life (t½) of Sugammadex [Part A]

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    End point title
    		 Plasma Half-Life (t½) of Sugammadex [Part A] [5]
    End point description
    The t½ of sugammadex, defined as the time required for the plasma concentration to decrease to 50% of maximum, was determined in each Part A arm. All participants with ≥5 post-dosing samples available are included.
    End point type
    Primary
    End point timeframe
    2 minutes (min), 15 min, 30 min, 60 min, 4-6 hours (hrs), and 10 hrs post-dose
    Notes
    [5] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years)
    Number of subjects analysed
    9
    5
    4
    8
    6
    6
    Units: Hours
        median (full range (min-max))
    1.15 (0.964 to 1.64)
    1.19 (1.01 to 1.71)
    1.49 (1.17 to 1.91)
    1.12 (0.922 to 1.78)
    1.56 (1.21 to 3.06)
    1.51 (1.20 to 1.91)
    No statistical analyses for this end point

    Primary: Percentage of Participants with ≥1 Adverse Event (AE) [Parts A and B]

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    End point title
    		 Percentage of Participants with ≥1 Adverse Event (AE) [Parts A and B] [6] [7]
    End point description
    The percentage of participants with ≥1 AE(s) for up to 7 days after treatment was determined for each treatment group, pooled according to treatment received. An AE is defined as any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Each participant who received a dose of study drug is included.
    End point type
    Primary
    End point timeframe
    Up to 7 days
    Notes
    [6] - 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: Per protocol, only descriptive statistics were determined.
    [7] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part B: Neostigmine + (Glycopyrrolate or Atropine) Parts A and B: Sugammadex 2 mg Parts A and B: Sugammadex 4 mg
    Number of subjects analysed
    34
    51
    191
    Units: Percentage of Participants
        number (not applicable)
    97.1
    78.4
    74.9
    No statistical analyses for this end point

    Primary: Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B]

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    End point title
    		 Time to Recovery of Participant Train-of-Four (TOF) Ratio to ≥0.9 [Part B] [8]
    End point description
    The time to recovery of TOF ratio to ≥0.9 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. All randomized participants in Part B who received ≥1 dose of study drug are included. Per protocol, the efficacy analysis is based on comparison of the Part B: Sugammadex 2 mg arm versus the Part B: Neostigmine + (Glycopyrrolate or Atropine) arm.
    End point type
    Primary
    End point timeframe
    Up to 30 minutes post-dose
    Notes
    [8] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part B: Sugammadex 2 mg/kg Part B: Sugammadex 4 mg/kg Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Number of subjects analysed
    33
    169
    34
    Units: Minutes
        geometric mean (confidence interval 95%)
    1.6 (1.3 to 2.0)
    1.9 (1.7 to 2.2)
    7.5 (5.6 to 10.0)
    Statistical analysis title
    		 Ratio of Geometric Means
    Comparison groups
    Part B: Sugammadex 2 mg/kg v Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 GM Ratio (SUG 2 mg / NEO + [GLY or ATR])
    Point estimate
    0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 0.32

    Secondary: Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B]

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    End point title
    		 Time to Recovery of Participant TOF Ratio to ≥0.7 [Part B] [9]
    End point description
    The time to recovery of TOF ratio to ≥0.7 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. All randomized participants in Part B who received ≥1 dose of study drug are included.
    End point type
    Secondary
    End point timeframe
    Up to 30 minutes post-dose
    Notes
    [9] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part B: Sugammadex 2 mg/kg Part B: Sugammadex 4 mg/kg Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Number of subjects analysed
    33
    169
    34
    Units: Minutes
        geometric mean (confidence interval 95%)
    1.1 (0.9 to 1.3)
    1.3 (1.1 to 1.4)
    3.7 (2.9 to 4.8)
    No statistical analyses for this end point

    Secondary: Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B]

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    End point title
    		 Time to Recovery of Participant TOF Ratio to ≥0.8 [Part B] [10]
    End point description
    The time to recovery of TOF ratio to ≥0.8 after administration of study intervention was determined for each Part B arm. The TOF ratio is the ratio of the magnitude of the fourth (T4) and first (T1) thumb twitches elicited by 4 electrical stimulations of the ulnar nerve, indicating the current degree of NMB as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Values closer to 1 indicate less NMB. All randomized participants in Part B who received ≥1 dose of study drug are included.
    End point type
    Secondary
    End point timeframe
    Up to 30 minutes post-dose
    Notes
    [10] - 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: Per protocol, only descriptive statistics were determined.
    End point values
    		 Part B: Sugammadex 2 mg/kg Part B: Sugammadex 4 mg/kg Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Number of subjects analysed
    33
    169
    34
    Units: Minutes
        geometric mean (confidence interval 95%)
    1.3 (1.1 to 1.6)
    1.5 (1.3 to 1.7)
    5.0 (3.8 to 6.7)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 14 days
    Adverse event reporting additional description
    An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. All participants who received ≥1 dose of study drug are included.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Part A: Sugammadex 2 mg (2 to <6 years)
    Reporting group description
    		 -

    Reporting group title
    Part A: Sugammadex 2 mg (6 to <12 years)
    Reporting group description
    		 -

    Reporting group title
    Part A: Sugammadex 2 mg (12 to <17 years)
    Reporting group description
    		 -

    Reporting group title
    Part A: Sugammadex 4 mg (2 to <6 years)
    Reporting group description
    		 -

    Reporting group title
    Part A: Sugammadex 4 mg (6 to <12 years)
    Reporting group description
    		 -

    Reporting group title
    Part A: Sugammadex 4 mg (12 to <17 years)
    Reporting group description
    		 -

    Reporting group title
    Part B: Sugammadex 2 mg
    Reporting group description
    		 -

    Reporting group title
    Part B: Sugammadex 4 mg
    Reporting group description
    		 -

    Reporting group title
    Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Reporting group description
    		 -

    Serious adverse events
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years) Part B: Sugammadex 2 mg Part B: Sugammadex 4 mg Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    3 / 33 (9.09%)
    3 / 169 (1.78%)
    2 / 34 (5.88%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Post procedural bile leak
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 33 (3.03%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 33 (3.03%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Respiratory, thoracic and mediastinal disorders
    Laryngospasm
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    1 / 34 (2.94%)
         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
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 33 (3.03%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    1 / 34 (2.94%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A: Sugammadex 2 mg (2 to <6 years) Part A: Sugammadex 2 mg (6 to <12 years) Part A: Sugammadex 2 mg (12 to <17 years) Part A: Sugammadex 4 mg (2 to <6 years) Part A: Sugammadex 4 mg (6 to <12 years) Part A: Sugammadex 4 mg (12 to <17 years) Part B: Sugammadex 2 mg Part B: Sugammadex 4 mg Part B: Neostigmine + (Glycopyrrolate or Atropine)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 9 (88.89%)
    3 / 5 (60.00%)
    2 / 4 (50.00%)
    8 / 10 (80.00%)
    5 / 6 (83.33%)
    6 / 6 (100.00%)
    26 / 33 (78.79%)
    117 / 169 (69.23%)
    29 / 34 (85.29%)
    Investigations
    Body temperature increased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Injury, poisoning and procedural complications
    Cardiac procedure complication
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Incision site pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    1 / 4 (25.00%)
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    2 / 33 (6.06%)
    5 / 169 (2.96%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    2
    5
    1
    Incision site swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Postoperative respiratory failure
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Procedural nausea
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    1 / 4 (25.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    3 / 33 (9.09%)
    9 / 169 (5.33%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    3
    9
    0
    Procedural pain
         subjects affected / exposed
    4 / 9 (44.44%)
    3 / 5 (60.00%)
    1 / 4 (25.00%)
    7 / 10 (70.00%)
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    22 / 33 (66.67%)
    98 / 169 (57.99%)
    24 / 34 (70.59%)
         occurrences all number
    4
    3
    1
    7
    3
    3
    22
    109
    25
    Procedural site reaction
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 5 (20.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Procedural vomiting
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    1 / 4 (25.00%)
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 33 (6.06%)
    4 / 169 (2.37%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    2
    4
    1
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 5 (20.00%)
    0 / 4 (0.00%)
    1 / 10 (10.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 33 (3.03%)
    9 / 169 (5.33%)
    3 / 34 (8.82%)
         occurrences all number
    2
    1
    0
    1
    1
    1
    1
    9
    3
    Pericardial effusion
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Sinus bradycardia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 33 (3.03%)
    1 / 169 (0.59%)
    2 / 34 (5.88%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    1
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 33 (3.03%)
    2 / 169 (1.18%)
    1 / 34 (2.94%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    1
    2
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    3
    Eye disorders
    Eye irritation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 33 (6.06%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 5 (20.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    1 / 169 (0.59%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Mouth swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 5 (40.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 33 (3.03%)
    10 / 169 (5.92%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    10
    2
    Palatal swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 5 (20.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    3 / 33 (9.09%)
    20 / 169 (11.83%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    3
    22
    2
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    3 / 169 (1.78%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    3
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    2 / 169 (1.18%)
    0 / 34 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    2
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Pain in extremity
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Infections and infestations
    Cystitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Postoperative wound infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 5 (0.00%)
    0 / 4 (0.00%)
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 33 (0.00%)
    0 / 169 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    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
    18 Apr 2017
    AM1: The primary purposes of the amendment were to update safety definitions regarding treatment-emergent bradycardia and to add text regarding trial stopping criteria.

    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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    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.

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