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    Clinical Trial Results:
    Randomized, Double-Blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of Retosiban Versus Placebo for Women in Spontaneous Preterm Labor

    Summary
    EudraCT number
    2014-003326-41
    Trial protocol
    GB   IT  
    Global end of trial date
    24 Jul 2017

    Results information
    Results version number
    v5(current)
    This version publication date
    30 Aug 2018
    First version publication date
    07 Feb 2018
    Other versions
    v1 , v2 , v3 , v4
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    200719
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000162-PIP20-16
    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
    06 Nov 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Jul 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To demonstrate the superiority of retosiban to prolong pregnancy and improve neonatal outcomes compared with placebo
    Protection of trial subjects
    Not applicable
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    29 Feb 2016
    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
    United Kingdom: 3
    Country: Number of subjects enrolled
    Japan: 8
    Country: Number of subjects enrolled
    United States: 14
    Worldwide total number of subjects
    25
    EEA total number of subjects
    3
    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)
    1
    Adults (18-64 years)
    24
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    NEWBORN-1 was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to investigate efficacy and safety of retosiban in female participants aged 12 to 45 years with an uncomplicated singleton pregnancy in preterm labor with intact membranes between 24 0/7 and 33 6/7 weeks gestation. The study was conducted in 3 countries.

    Pre-assignment
    Screening details
    Twenty-five participants were randomly assigned to study treatments: 12 participants to retosiban intravenous (IV) infusion and 13 participants to matched placebo IV infusion. Two participants randomized to retosiban arm did not receive study treatment. The study was terminated early due to feasibility of recruiting the study in a timely manner.

    Pre-assignment period milestones
    Number of subjects started
    25
    Intermediate milestone: Number of subjects
    Treated: 23
    Number of subjects completed
    23

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Randomized and not treated: 2
    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, IV loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo was 0.9 percent sodium chloride matched for retosiban loading dose and continuous infusion rates.

    Arm title
    Retosiban
    Arm description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    Retosiban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Retosiban was available as a clear, colorless solution for infusion at a concentration of 15 milligrams per milliliter (mg/mL).

    Number of subjects in period 1 [1]
    Placebo Retosiban
    Started
    13
    10
    Completed
    13
    10
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Two participants randomized to retosiban arm did not receive study treatment due to labor progression.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, IV loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.

    Reporting group title
    Retosiban
    Reporting group description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period.

    Reporting group values
    Placebo Retosiban Total
    Number of subjects
    13 10
    Age categorical
    Units: Subjects
    Age continuous
    Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment.
    Units: years
        arithmetic mean (standard deviation)
    26.5 ± 6.78 27.7 ± 6.73 -
    Gender categorical
    Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment.
    Units: Subjects
        Female
    13 10 23
        Male
    0 0 0
    Race/Ethnicity, Customized
    Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment.
    Units: Subjects
        African American/African Heritage
    2 2 4
        Asian-Central/South Asian Heritage
    0 1 1
        Asian-East Asian Heritage
    1 0 1
        Asian-Japanese Heritage
    4 2 6
        Asian-South East Asian Heritage
    1 0 1
        White-White/Caucasian/European Heritage
    5 5 10

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, IV loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.

    Reporting group title
    Retosiban
    Reporting group description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period.

    Subject analysis set title
    Retosiban
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771). Actual total participants analyzed is 53 and not 10. 53 cannot be added due to system limitation.

    Primary: Time to delivery or treatment failure, whichever occurs first

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    End point title
    Time to delivery or treatment failure, whichever occurs first [1]
    End point description
    Time to delivery or treatment failure is the number of days from the first dose of study treatment until delivery or treatment failure whichever occurs first. Treatment failure is defined as the administration of any putative tocolytic medication for treatment of preterm labor or as prophylaxis of preterm labor. Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment. The mean number of days to delivery or treatment failure along with standard deviation has been presented. Statistical analysis was not performed due to early termination of the study and resultant small sample size.
    End point type
    Primary
    End point timeframe
    Up to 17 weeks
    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 was not performed due to early termination of the study and resultant small sample size.
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [2]
    10 [3]
    Units: Days
    arithmetic mean (standard deviation)
        Days
    11.10 ± 14.987
    18.91 ± 22.993
    Notes
    [2] - Maternal ITT Population
    [3] - Maternal ITT Population
    No statistical analyses for this end point

    Primary: Number of neonates with any diagnosis from the neonatal morbidity and mortality composite component

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    End point title
    Number of neonates with any diagnosis from the neonatal morbidity and mortality composite component [4]
    End point description
    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, respiratory distress syndrome (RDS), bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, intraventricular hemorrhage (IVH), white matter injury and cerebellar hemorrhage. Neonates with any of the composite component has been presented. Statistical analysis was not performed due to early termination of study and resultant small sample size. Neonatal ITT Population comprised of all neonates whose mothers were the randomized participants who have been exposed to study treatment, that is, mothers from the ITT Population.
    End point type
    Primary
    End point timeframe
    Up to 28 days after the estimated date of delivery (EDD) of 40 0/7 weeks
    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: Statistical analysis was not performed due to early termination of the study and resultant small sample size.
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [5]
    10 [6]
    Units: Participants
        Participants
    4
    2
    Notes
    [5] - Neonatal ITT Population
    [6] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Time to delivery

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    End point title
    Time to delivery
    End point description
    The time to delivery was calculated as the days between the delivery and start time of the study treatment infusion using the formula: Time to delivery (days) = (date and time of delivery minus date and time of start of infusion) divided by (24 multiplied by 60). The mean number of days to delivery along with standard deviation has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [7]
    10 [8]
    Units: Days
    arithmetic mean (standard deviation)
        Days
    16.32 ± 18.595
    19.18 ± 22.770
    Notes
    [7] - Maternal ITT Population
    [8] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births prior to 37 0/7 Weeks gestation

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    End point title
    Number of participants with births prior to 37 0/7 Weeks gestation
    End point description
    Gestational age at birth (weeks) is defined as the gestational age when the baby is born. Participants were considered to have delivered prior to 37 0/7 weeks, that is preterm, if the gestational age at birth is less than 37 0/7 weeks. The number of participants who delivered prior to 37 0/7 weeks gestation has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 13 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [9]
    10 [10]
    Units: Participants
        Participants
    9
    8
    Notes
    [9] - Maternal ITT Population
    [10] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births at term

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    End point title
    Number of participants with births at term
    End point description
    Participants were considered to have delivered at term if the gestational age was >=37 0/7. The number of participants who delivered at term, that is, 37 0/7 to 41 6/7 weeks gestation has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [11]
    10 [12]
    Units: Participants
        Participants
    4
    2
    Notes
    [11] - Maternal ITT Population
    [12] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Length of neonatal hospital stay

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    End point title
    Length of neonatal hospital stay
    End point description
    The length of stay was collected from medical records and was calculated as the days between the delivery date and time and discharge date and time.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD of 40 0/7 weeks gestation
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [13]
    10 [14]
    Units: Days
    arithmetic mean (standard deviation)
        Days
    37.50 ± 34.537
    26.05 ± 32.689
    Notes
    [13] - Neonatal ITT Population
    [14] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births prior to 35 0/7 weeks gestation

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    End point title
    Number of participants with births prior to 35 0/7 weeks gestation
    End point description
    The number of participants who delivered prior to 35 0/7 weeks gestation has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 11 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [15]
    10 [16]
    Units: Participants
        Participants
    9
    7
    Notes
    [15] - Maternal ITT Population
    [16] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births prior to 32 0/7 weeks gestation

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    End point title
    Number of participants with births prior to 32 0/7 weeks gestation
    End point description
    The number of participants who delivered prior to 32 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 32 0/7 week's gestation and delivered were included.
    End point type
    Secondary
    End point timeframe
    Up to 8 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    9 [17]
    6 [18]
    Units: Participants
        Participants
    6
    2
    Notes
    [17] - Maternal ITT Population
    [18] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births prior to 28 0/7 weeks gestation

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    End point title
    Number of participants with births prior to 28 0/7 weeks gestation
    End point description
    The number of participants who delivered prior to 28 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 28 0/7 week's gestation and delivered were included.
    End point type
    Secondary
    End point timeframe
    Up to 4 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    2 [19]
    2 [20]
    Units: Participants
        Participants
    2
    1
    Notes
    [19] - Maternal ITT Population
    [20] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births at <=7 days from the first study treatment

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    End point title
    Number of participants with births at <=7 days from the first study treatment
    End point description
    The number of participants who delivered in less than or equal to 7 days from first dose of study treatment has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 7 days
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [21]
    10 [22]
    Units: Participants
        Participants
    5
    5
    Notes
    [21] - Maternal ITT Population
    [22] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births at <=48 hours from the first study treatment

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    End point title
    Number of participants with births at <=48 hours from the first study treatment
    End point description
    The number of participants who delivered in less than or equal to 48 hours from first dose of study treatment has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 48 hours
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [23]
    10 [24]
    Units: Participants
        Participants
    3
    3
    Notes
    [23] - Maternal ITT Population
    [24] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with births at <=24 hours from the first study treatment

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    End point title
    Number of participants with births at <=24 hours from the first study treatment
    End point description
    The number of participants who delivered in less than or equal to 24 hours from first dose of study treatment has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [25]
    10 [26]
    Units: Participants
        Participants
    3
    1
    Notes
    [25] - Maternal ITT Population
    [26] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of neonates with any of the co-primary composite neonatal morbidity and mortality, excluding RDS

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    End point title
    Number of neonates with any of the co-primary composite neonatal morbidity and mortality, excluding RDS
    End point description
    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, IVH, white matter injury and cerebellar hemorrhage. The number of neonates with any co-primary composite neonatal morbidity and mortality component, excluding RDS has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 weeks after EDD (40 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [27]
    10 [28]
    Units: Participants
        Participants
    3
    0
    Notes
    [27] - Neonatal ITT Population
    [28] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Number of neonates with each individual component of the composite neonatal morbidity and mortality

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    End point title
    Number of neonates with each individual component of the composite neonatal morbidity and mortality
    End point description
    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, bronchopulmonary dysplasia, necrotizing enterocolitis or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity, IVH, white matter injury and cerebellar hemorrhage. The number of neonates with each individual component of the composite component has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 days after the EDD of 40 0/7 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [29]
    10 [30]
    Units: Participants
        Fetal Death
    0
    0
        Neonatal Death
    0
    0
        RDS
    3
    2
        Bronchopulmonary dysplasia
    3
    0
        Necrotizing enterocolitis or Isolated Perforation
    0
    0
        Sepsis
    0
    0
        Meningitis
    0
    0
        Retinopathy of prematurity
    0
    0
        IVH
    0
    0
        White Matter Injury
    0
    0
        Cerebellar Hemorrhage
    0
    0
    Notes
    [29] - Neonatal ITT Population
    [30] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Number of neonatal participants with admission to a particular hospital unit

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    End point title
    Number of neonatal participants with admission to a particular hospital unit
    End point description
    Neonatal healthcare resource utilization was collected from review of medical records. The number of neonatal participants who were admitted to a particular hospital unit that is, level III (or higher) intensive neonatal care (NICU), Intensive care unit (ICU), general ward, Level I - Basic Neonatal care, Well born nursery (SCBU) and Level II-Special Care Newborn nursery high dependency (NHDU) has been summarized. Neonatal Safety Population consisted of neonates whose mothers received study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [31]
    10 [32]
    Units: Participants
        Level III (or higher) NICU
    5
    6
        Intensive care unit
    0
    1
        General Ward
    2
    2
        Level II-Special Care NHDU
    0
    1
        Missing
    1
    0
        Multiple ward type
    5
    0
    Notes
    [31] - Neonatal Safety Population
    [32] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Length of stay in specialized care unit

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    End point title
    Length of stay in specialized care unit
    End point description
    Neonatal healthcare resource utilization was collected from review of medical records. The length of stay in a specialized care unit (NICU or ICU) has been presented for neonatal participants with admission to ICU or NICU.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    10 [33]
    7 [34]
    Units: Days
    arithmetic mean (standard deviation)
        Days
    40.34 ± 35.475
    35.60 ± 35.308
    Notes
    [33] - Neonatal Safety Population
    [34] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Number of newborn participants with hospital readmission

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    End point title
    Number of newborn participants with hospital readmission
    End point description
    Newborn hospital readmission following hospitalization for birth was collected from the newborn's medical records. The number of newborn participants who had readmission to hospital is presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 days of EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [35]
    10 [36]
    Units: Participants
        Participants
    0
    0
    Notes
    [35] - Neonatal Safety Population
    [36] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Length of stay following readmission to hospital

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    End point title
    Length of stay following readmission to hospital
    End point description
    Newborn hospital readmission following hospitalization for birth was collected from the newborn's medical records. Length of stay in hospital following readmission is presented for neonates.
    End point type
    Secondary
    End point timeframe
    Up to 28 days after EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [37]
    10 [38]
    Units: Days
    median (full range (min-max))
        Days
    0 (0 to 0)
    0 (0 to 0)
    Notes
    [37] - Neonatal Safety Population
    [38] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with ambulatory surgery

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    End point title
    Number of participants with ambulatory surgery
    End point description
    Information regarding participants who had ambulatory surgery was collected from the newborn medical records. The number of neonatal participants with ambulatory surgery is presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [39]
    10 [40]
    Units: Participants
        Participants
    0
    0
    Notes
    [39] - Neonatal Safety Population
    [40] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Time to treatment failure

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    End point title
    Time to treatment failure
    End point description
    Treatment failure is defined as the administration of any putative tocolytic medication for treatment of preterm labor or as prophylaxis of preterm labor. Time to treatment failure is the number of days from the first dose of study treatment until treatment failure. The mean number of days to delivery or treatment failure along with standard deviation has been presented. Only those maternal participants with treatment failure were included in the analysis. 99999 indicates standard deviation could not be calculated as only one participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    4 [41]
    1 [42]
    Units: Days
    arithmetic mean (standard deviation)
        Days
    1.141 ± 1.4307
    0.899 ± 99999
    Notes
    [41] - Maternal ITT Population
    [42] - Maternal ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants who received any putative tocolytic

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    End point title
    Number of participants who received any putative tocolytic
    End point description
    A putative tocolytic medication was the medication administered for active preterm labor or as prevention of preterm labor and included calcium channel blockers, nonsteroidal anti-inflammatory drugs, or beta agonists, or magnesium sulfate doses that exceeded prespecified IV loading doses, infusion rates, or total duration of administration.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [43]
    10 [44]
    Units: Participants
        Participants
    4
    1
    Notes
    [43] - Maternal Safety Population
    [44] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with subsequent preterm labor

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    End point title
    Number of participants with subsequent preterm labor
    End point description
    The participants who had not delivered after 48 hours post-infusion were contacted to determine if they had delivered or experienced any subsequent episodes of preterm labor. A subsequent episode of preterm labor was only recorded if the participant reported it to the Principal Investigator during one of the telephone follow-up calls but did not then go on to immediately deliver. However, if labor started and led to immediate delivery, then the only data collected would be the pre-specified delivery data and thus would not be counted as a subsequent episode of preterm labor. The number of participants who had a subsequent episode of preterm labor after administration of the study treatment has been presented. Maternal Safety Population comprised of all maternal participants randomly assigned to treatment who have been exposed to study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 11 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [45]
    10 [46]
    Units: Participants
        Participants
    1
    1
    Notes
    [45] - Maternal Safety Population
    [46] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of maternal participants with adverse events (AEs) and serious adverse events (SAEs)

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    End point title
    Number of maternal participants with adverse events (AEs) and serious adverse events (SAEs)
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that mey require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. The number of maternal participants who experienced at least one AE and one SAE has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 6 weeks after delivery
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [47]
    10 [48]
    Units: Participants
        AEs
    6
    6
        SAEs
    0
    0
    Notes
    [47] - Maternal Safety Population
    [48] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP)

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    End point title
    Change from Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP)
    End point description
    SBP and DBP were measured with participants in a semirecumbent or seated position. SBP and DBP were measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 9 days
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [49]
    10 [50]
    Units: millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        DBP; Day 1: 15 to 30 minutes; n=13, 10
    -3.2 ± 10.64
    -6.8 ± 8.22
        DBP; Day 1: 4 to 8 hours; n=11, 10
    -9.0 ± 11.31
    -7.0 ± 10.14
        DBP; Day 1: 20 to 24 hours; n=10, 8
    -13.1 ± 11.05
    -6.5 ± 8.65
        DBP; Day 2; n=11, 7
    -10.2 ± 11.07
    -4.0 ± 6.66
        DBP; Post infusion assessment; n=9, 5
    -6.6 ± 12.69
    -2.8 ± 4.76
        SBP; Day 1: 15 to 30 minutes; n=13, 10
    -0.8 ± 7.50
    -3.1 ± 10.40
        SBP; Day 1: 4 to 8 hours; n=11, 10
    -7.1 ± 13.09
    -1.3 ± 9.06
        SBP; Day 1: 20 to 24 hours; n=10, 8
    -5.2 ± 12.47
    2.6 ± 14.56
        SBP; Day 2; n=11, 7
    -4.5 ± 11.86
    0.7 ± 10.21
        SBP; Post infusion assessment; n=9, 5
    -9.6 ± 8.69
    -7.0 ± 8.22
    Notes
    [49] - Maternal Safety Population
    [50] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in heart rate

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    End point title
    Change from Baseline in heart rate
    End point description
    Heart rate was measured with the participants in a semirecumbent or seated position. Heart rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 9 days
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [51]
    10 [52]
    Units: beats per minute
    arithmetic mean (standard deviation)
        Day 1: 15 to 30 minutes; n=13, 10
    -5.1 ± 12.37
    1.4 ± 8.13
        Day 1: 4 to 8 hours; n=11, 10
    -2.6 ± 10.82
    -0.3 ± 8.12
        Day 1: 20 to 24 hours; n=9, 8
    -4.1 ± 10.61
    6.5 ± 21.64
        Day 2; n=11, 7
    -5.6 ± 15.73
    -3.6 ± 13.91
        Post infusion assessment; n=9, 5
    -6.1 ± 17.80
    -3.8 ± 16.24
    Notes
    [51] - Maternal Safety Population
    [52] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in temperature

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    End point title
    Change from Baseline in temperature
    End point description
    Temperature was measured with the participants in a semirecumbent or seated position. Temperature was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [53]
    10 [54]
    Units: degree Celsius
    arithmetic mean (standard deviation)
        Day 1: 15 to 30 minutes; n=12, 9
    -0.028 ± 0.4123
    -0.111 ± 0.1900
        Day 1: 4 to 8 hours; n=11, 10
    0.087 ± 0.3947
    -0.144 ± 0.3594
        Day 1: 20 to 24 hours; n=10, 8
    0.104 ± 0.5413
    -0.043 ± 0.3174
        Day 2; n=11, 7
    0.105 ± 0.5067
    0.051 ± 0.2062
        Post-infusion assessment; n=9, 5
    -0.136 ± 0.4668
    0.072 ± 0.2234
    Notes
    [53] - Maternal Safety Population
    [54] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in respiratory rate

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    End point title
    Change from Baseline in respiratory rate
    End point description
    Respiratory rate was measured with the participants in a semirecumbent or seated position. Respiratory rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [55]
    10 [56]
    Units: breaths per minute
    arithmetic mean (standard deviation)
        Day 1: 15 to 30 minutes; n=11, 8
    0.5 ± 3.45
    -1.1 ± 2.90
        Day 1: 4 to 8 hours; n=8, 9
    1.1 ± 3.83
    -1.1 ± 2.15
        Day 1: 20 to 24 hours; n=9, 7
    0.3 ± 2.35
    -1.0 ± 2.77
        Day 2; n=10, 6
    0.9 ± 4.01
    0.0 ± 1.79
        Post infusion assessment; n=8, 4
    0.4 ± 4.27
    0.5 ± 2.52
    Notes
    [55] - Maternal Safety Population
    [56] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematocrit levels

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    End point title
    Change from Baseline in hematocrit levels
    End point description
    Blood samples were collected for the evaluation of change in hematocrit levels from Baseline. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [57]
    10 [58]
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        Day 2; n=9, 3
    -0.0343 ± 0.04324
    -0.0470 ± 0.02773
        Post-infusion assessment; n=7, 5
    -0.0090 ± 0.02900
    -0.0078 ± 0.02928
    Notes
    [57] - Maternal Safety Population
    [58] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hemoglobin and Erythrocyte Mean Corpuscular hemoglobin Concentration (MCHC)

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    End point title
    Change from Baseline in hemoglobin and Erythrocyte Mean Corpuscular hemoglobin Concentration (MCHC)
    End point description
    Blood samples were collected for the evaluation of change in hemoglobin levels and MCHC from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [59]
    10 [60]
    Units: grams per liter (g/L)
    arithmetic mean (standard deviation)
        Hemoglobin; Day 2; n=9, 3
    -11.2 ± 11.20
    -15.7 ± 6.66
        Hemoglobin; Post-infusion assessment; n=7, 5
    -1.0 ± 9.76
    -1.6 ± 8.79
        MCHC; Day 2; n=9, 3
    -0.3 ± 17.27
    -2.7 ± 10.97
        MCHC; Post-infusion assessment; n=7, 5
    5.0 ± 8.52
    2.6 ± 5.41
    Notes
    [59] - Maternal Safety Population
    [60] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes count

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    End point title
    Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes count
    End point description
    Blood samples were collected for the evaluation of change in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes count. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [61]
    10 [62]
    Units: Billion cells per liter (L)
    arithmetic mean (standard deviation)
        Basophils; Day 2; n=9, 3
    -0.003 ± 0.0132
    0.000 ± 0.0458
        Basophils; post-infusion assessment; n=7, 5
    0.003 ± 0.0160
    0.058 ± 0.1103
        Eosinophils; Day 2; n=9, 3
    0.004 ± 0.0938
    -0.063 ± 0.0513
        Eosinophils; post-infusion assessment; 7, 5
    0.064 ± 0.1321
    -0.044 ± 0.1328
        Lymphocytes; Day 2; n=9, 3
    0.323 ± 0.6117
    0.877 ± 0.1914
        Lymphocytes; post-infusion assessment; 7, 5
    0.253 ± 1.0579
    1.006 ± 1.4223
        Monocytes; Day 2; n=9, 3
    0.008 ± 0.3389
    0.147 ± 0.5773
        Monocytes; post-infusion assessment; 7, 5
    0.141 ± 0.2535
    -0.082 ± 0.4135
        Neutrophils; Day 2; n=9, 3
    2.744 ± 6.9362
    -1.813 ± 3.3001
        Neutrophils; post-infusion assessment; 7, 5
    -2.246 ± 6.0323
    -1.910 ± 2.8497
        Platelets; Day 2; n=8, 3
    -6.4 ± 47.42
    -24.7 ± 32.58
        Platelets; post-infusion assessment; 6, 5
    -15.7 ± 60.48
    -5.4 ± 33.34
        Leukocytes; Day 2; n=9, 3
    3.10 ± 6.720
    -0.87 ± 2.914
        Leukocytes; post-infusion assessment; 7, 5
    -1.76 ± 5.358
    -0.98 ± 2.645
    Notes
    [61] - Maternal Safety Population
    [62] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in erythrocyte mean corpuscular volume (MCV) and mean platelet volume (MPV)

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    End point title
    Change from Baseline in erythrocyte mean corpuscular volume (MCV) and mean platelet volume (MPV)
    End point description
    Blood samples were collected for the evaluation of change in MCV and MPV from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [63]
    10 [64]
    Units: femtoliter (fL)
    arithmetic mean (standard deviation)
        MCV; Day 2; n=9, 3
    0.4 ± 2.79
    1.7 ± 4.73
        MCV; Post-infusion assessment; n=7, 5
    -1.9 ± 1.77
    -0.8 ± 1.30
        MPV; Day 2; n=8, 3
    -0.11 ± 0.455
    -0.20 ± 0.436
        MPV; Post-infusion assessment; n=6, 5
    0.02 ± 0.833
    0.48 ± 1.026
    Notes
    [63] - Maternal Safety Population
    [64] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in erythrocyte level

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    End point title
    Change from Baseline in erythrocyte level
    End point description
    Blood samples were collected for the evaluation of change in erythrocyte level from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [65]
    10 [66]
    Units: Trillion cells per liter
    arithmetic mean (standard deviation)
        Day 2; n=9, 3
    -0.39 ± 0.423
    -0.53 ± 0.153
        Post-infusion assessment; n=7, 5
    -0.03 ± 0.330
    -0.02 ± 0.303
    Notes
    [65] - Maternal Safety Population
    [66] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) levels

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    End point title
    Change from Baseline in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) levels
    End point description
    Blood samples were collected for the evaluation of change in ALP, ALT, AST, GGT and LDH from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [67]
    10 [68]
    Units: International Units per liter (IU/L)
    arithmetic mean (standard deviation)
        ALP; Day 2; n=9, 5
    -17.3 ± 17.56
    -11.8 ± 6.46
        ALP; post-infusion assessment; n=8, 6
    6.6 ± 31.14
    -2.8 ± 14.08
        ALT; Day 2; n=9, 5
    3.9 ± 19.60
    4.4 ± 10.64
        ALT; post-infusion assessment; n=8, 6
    -8.8 ± 20.04
    2.5 ± 5.50
        AST; Day 2; n=9, 5
    4.4 ± 15.69
    2.0 ± 10.20
        AST; post-infusion assessment; n=8, 6
    -9.1 ± 13.05
    -0.5 ± 7.45
        GGT; Day 2; n=9, 5
    -0.9 ± 1.69
    -0.8 ± 1.30
        GGT; post-infusion assessment; n=7, 5
    4.4 ± 2.57
    0.4 ± 2.07
        LDH; Day 2; n=9, 5
    -6.7 ± 33.51
    -26.4 ± 31.86
        LDH; post-infusion assessment; n=7, 5
    -8.1 ± 21.93
    -7.6 ± 31.76
    Notes
    [67] - Maternal Safety Population
    [68] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in albumin and protein levels

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    End point title
    Change from Baseline in albumin and protein levels
    End point description
    Blood samples were collected for the evaluation of change in albumin and protein levels from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [69]
    10 [70]
    Units: grams per liter (g/L)
    arithmetic mean (standard deviation)
        Albumin; Day 2; n=9, 5
    -3.4 ± 3.68
    -2.6 ± 1.67
        Albumin; post-infusion assessment; n=7, 5
    -1.3 ± 2.21
    -1.0 ± 2.35
        Protein; Day 2; n=9, 5
    -5.8 ± 6.26
    -5.4 ± 3.58
        Protein; post-infusion assessment; n=7, 5
    -2.4 ± 3.41
    -1.8 ± 5.02
    Notes
    [69] - Maternal Safety Population
    [70] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in anion gap, calcium, chloride, carbon dioxide, glucose, potassium, magnesium, phosphate and sodium level

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    End point title
    Change from Baseline in anion gap, calcium, chloride, carbon dioxide, glucose, potassium, magnesium, phosphate and sodium level
    End point description
    Blood samples were collected for the evaluation of change from Baseline in levels of anion gap, calcium, chloride, carbon dioxide, glucose, potassium, magnesium, phosphate, and sodium. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [71]
    10 [72]
    Units: millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        Anion Gap; Day 2; n=8, 4
    0.0 ± 4.72
    0.0 ± 1.83
        Anion Gap; post-infusion assessment; n=7, 4
    -1.6 ± 5.26
    0.3 ± 2.22
        Calcium; Day 2; n=9, 5
    -0.042 ± 0.2833
    -0.040 ± 0.1208
        Calcium; post-infusion assessment; n=7, 5
    0.091 ± 0.2052
    -0.048 ± 0.1016
        Chloride; Day 2; n=9, 5
    1.0 ± 5.17
    1.8 ± 2.17
        Chloride; post-infusion assessment; n=7, 5
    -0.7 ± 3.35
    -0.6 ± 2.30
        Carbon Dioxide; Day 2; n=9, 5
    -0.2 ± 3.63
    0.0 ± 2.35
        Carbon Dioxide; post-infusion assessment; n=7, 5
    2.3 ± 3.64
    -0.2 ± 2.77
        Glucose; Day 2; n=9, 5
    1.47 ± 1.639
    1.98 ± 1.064
        Glucose; post-infusion assessment; n=7, 5
    0.11 ± 2.497
    0.28 ± 2.109
        Potassium; Day 2; n=9, 5
    -0.16 ± 0.394
    0.10 ± 0.515
        Potassium; post-infusion assessment; n=7, 5
    -0.16 ± 0.237
    0.10 ± 0.283
        Magnesium; Day 2; n=9, 5
    -0.411 ± 0.9476
    -0.236 ± 0.5428
        Magnesium; post-infusion assessment; n=7, 5
    -0.449 ± 0.6473
    -0.056 ± 0.6199
        Phosphate; Day 2; n=9, 5
    -0.133 ± 0.1768
    0.030 ± 0.2928
        Phosphate; post-infusion assessment; n=7, 5
    0.021 ± 0.2018
    0.110 ± 0.1557
        Sodium; Day 2; n=9, 5
    1.4 ± 2.96
    0.4 ± 1.67
        Sodium; post-infusion assessment; n=7, 5
    0.1 ± 2.12
    -0.8 ± 1.64
    Notes
    [71] - Maternal Safety Population
    [72] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in direct bilirubin, bilirubin, indirect bilirubin, creatinine and urate levels

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    End point title
    Change from Baseline in direct bilirubin, bilirubin, indirect bilirubin, creatinine and urate levels
    End point description
    Blood samples were collected for the evaluation of change from Baseline in levels of direct bilirubin, bilirubin, indirect bilirubin, creatinine and urate. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
    End point type
    Secondary
    End point timeframe
    Baseline and up to 1 week
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [73]
    10 [74]
    Units: micromoles per liter (µmol/L)
    arithmetic mean (standard deviation)
        Direct Bilirubin; Day 2; n=9, 5
    0.0 ± 1.00
    -0.4 ± 0.89
        Direct Bilirubin; post-infusion assessment; n=7, 5
    0.3 ± 0.76
    -0.4 ± 0.89
        Bilirubin; Day 2; n=9, 5
    -0.7 ± 1.41
    -0.8 ± 1.10
        Bilirubin; post-infusion assessment; n=8, 6
    -0.3 ± 1.28
    -2.0 ± 3.10
        Indirect Bilirubin; Day 2; n=9, 5
    -0.7 ± 1.41
    -0.4 ± 1.67
        Indirect Bilirubin; post-infusion assessment;n=7,5
    -0.6 ± 1.51
    -1.6 ± 3.85
        Creatinine; Day 2; n=6, 3
    -0.33 ± 6.812
    2.37 ± 1.429
        Creatinine; post-infusion assessment; n=6, 3
    1.92 ± 5.075
    -0.33 ± 2.695
        Urate; Day 2; n=9, 5
    1.1 ± 24.72
    -22.0 ± 13.04
        Urate; post-infusion assessment; n=7, 5
    12.9 ± 24.30
    -2.0 ± 40.25
    Notes
    [73] - Maternal Safety Population
    [74] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants who discontinued study treatment due to clinical and laboratory toxicities

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    End point title
    Number of participants who discontinued study treatment due to clinical and laboratory toxicities
    End point description
    Number of maternal participants who discontinued study treatment due to clinical and laboratory toxicities is presented.
    End point type
    Secondary
    End point timeframe
    Up to 48 hours post-infusion
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [75]
    10 [76]
    Units: Participants
        Participants
    0
    0
    Notes
    [75] - Maternal Safety Population
    [76] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of maternal participants with a score of 12 or higher on the Edinburgh Postnatal Depression Scale (EPDS)

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    End point title
    Number of maternal participants with a score of 12 or higher on the Edinburgh Postnatal Depression Scale (EPDS)
    End point description
    The effect of preterm birth on maternal health status was assessed using the EPDS. The EPDS is a 10-item self-reported assessment of depression, validated for administration during both the antenatal and the post-natal periods. Items are rated on a 4-point variable Likert scale, ranging from 0 to 3. The total score was calculated by adding individual scores for each item and ranged from 0 to 30. A score of less than 8 indicates depression not likely; score of 9 to 11 indicates possible depression and a score of more than 12 indicates an increased probability of depression. Maternal participants were required to complete the EPDS at the maternal follow-up assessment 6 weeks post-delivery.
    End point type
    Secondary
    End point timeframe
    Up to 6 weeks post delivery
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [77]
    10 [78]
    Units: Participants
        Participants
    2
    0
    Notes
    [77] - Maternal Safety Population
    [78] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of maternal participants with AEs of special interest (AESI).

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    End point title
    Number of maternal participants with AEs of special interest (AESI).
    End point description
    Maternal AESI included: maternal death; chorioamnionitis and its complications (clinical chorioamnionitis, preterm premature rupture of membranes, endomyometritis, wound infection, pelvic abscess, bacteremia, septic shock, disseminated intravascular coagulation, and adult RDS); placental abruption; postpartum hemorrhage – postpartum hemorrhage and/or retained placenta and pulmonary edema. The number of participants with at least one AESI has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 6 weeks post-delivery
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [79]
    10 [80]
    Units: Participants
        Participants
    0
    1
    Notes
    [79] - Maternal Safety Population
    [80] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of maternal participants with disease related AEs (DRE)

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    End point title
    Number of maternal participants with disease related AEs (DRE)
    End point description
    Maternal DREs included: signs and symptoms of labor discomfort (example, cramping, backache, muscle aches, nausea); subsequent episodes of preterm labor and hospitalization for delivery. The number of participants with at least one DRE has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 6 weeks post-delivery
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [81]
    10 [82]
    Units: Participants
        Participants
    0
    1
    Notes
    [81] - Maternal Safety Population
    [82] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of fetal participants with AEs and SAEs prior to delivery

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    End point title
    Number of fetal participants with AEs and SAEs prior to delivery
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. Fetal AEs and SAEs included the adverse events that were experienced by the fetus prior to delivery. The number of participants who experienced at least one AE and one SAE has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks post-infusion
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [83]
    10 [84]
    Units: Participants
        AE
    3
    5
        SAE
    0
    1
    Notes
    [83] - Maternal Safety Population
    [84] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with fetal acidosis

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    End point title
    Number of participants with fetal acidosis
    End point description
    The number of participants with fetal acidosis is presented.
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [85]
    10 [86]
    Units: Participants
        Participants
    0
    0
    Notes
    [85] - Maternal Safety Population
    [86] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with fetal AESI

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    End point title
    Number of participants with fetal AESI
    End point description
    Fetal AESI included: intrauterine fetal demise; category II or III fetal heart rate tracing; and fetal inflammatory response syndrome characterized by cord blood interleukin-6 >11 picogram per milliliter (pg/mL), funisitis, or chorionic vasculitis. The number of participants who experienced at least one AESI has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [87]
    10 [88]
    Units: Participants
        Participants
    3
    5
    Notes
    [87] - Maternal Safety Population
    [88] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Neonatal APGAR Scores

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    End point title
    Neonatal APGAR Scores
    End point description
    APGAR is a quick test to assess the health of new born children. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two, then summing up the five values obtained. APGAR score ranges from 0 to 10 where a score of 7 and above is normal. The mean and standard deviation of APGAR scores at one minute and at five minutes of birth has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 5 minutes after birth
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [89]
    10 [90]
    Units: Score on APGAR scale
    arithmetic mean (standard deviation)
        one minute at birth
    7.3 ± 1.80
    7.5 ± 1.78
        five minutes at birth
    8.5 ± 1.05
    8.7 ± 1.06
    Notes
    [89] - Neonatal ITT Population
    [90] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Weight of neonates

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    End point title
    Weight of neonates
    End point description
    The weight of neonates was obtained from the neonate birth record. The mean weight of neonates and standard deviation has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [91]
    10 [92]
    Units: grams (g)
    arithmetic mean (standard deviation)
        grams (g)
    2015.0 ± 805.67
    2121.2 ± 681.31
    Notes
    [91] - Neonatal ITT Population
    [92] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Head circumference of neonates

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    End point title
    Head circumference of neonates
    End point description
    The head circumference was determined from the neonate birth record.
    End point type
    Secondary
    End point timeframe
    Up to 17 weeks
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [93]
    10 [94]
    Units: centimeters (cm)
    arithmetic mean (standard deviation)
        centimeters (cm)
    29.57 ± 2.791
    30.13 ± 3.059
    Notes
    [93] - Neonatal ITT Population
    [94] - Neonatal ITT Population
    No statistical analyses for this end point

    Secondary: Number of neonatal participants with AEs and SAEs

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    End point title
    Number of neonatal participants with AEs and SAEs
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. The number of participants who experienced at least one AE and one SAE has been presented. Neonatal Safety Population consisted of neonates whose mothers received randomized treatment.
    End point type
    Secondary
    End point timeframe
    Up to 28 days after the EDD of 40 weeks gestation
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [95]
    10 [96]
    Units: Participants
        AEs
    8
    7
        SAEs
    3
    5
    Notes
    [95] - Neonatal Safety Population
    [96] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Number of neonatal participants with AESI

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    End point title
    Number of neonatal participants with AESI
    End point description
    Neonatal AESI included: Neonatal death; Asphyxia; Infections (early onset neonatal sepsis, septic shock, pneumonia, meningitis); RDS; Hypotension; IVH/periventricular leukomalacia; Bronchopulmonary dysplasia; Neonatal acidosis; Hyperbilirubinemia; Necrotizing enterocolitis; and Hypoxic ischemic encephalopathy. The number of neonatal participants who experienced at least one AESI has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 days after EDD of 40 weeks gestation
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [97]
    10 [98]
    Units: Participants
        Participants
    8
    5
    Notes
    [97] - Neonatal Safety Population
    [98] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Number of neonatal participants with DRE

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    End point title
    Number of neonatal participants with DRE
    End point description
    The disease related neonatal events occurring in Infants born prior to 37 completed weeks included: apnea (severe), respiratory failure due to fatigue, hypoxia, or air leak from alveolar injury, patent ductus arteriosus, bradycardia, ventriculomegaly, cerebellar hemorrhage, hydrocephalus other than congenital, gastroesophageal reflux, aspiration pneumonia, anemia, retinopathy of prematurity (all stages), hearing disorder, temperature instability and hypoglycemia. The number of participants with at least one DRE has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 days after EDD of 40 weeks gestation
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [99]
    10 [100]
    Units: Participants
        Participants
    4
    2
    Notes
    [99] - Neonatal Safety Population
    [100] - Neonatal Safety Population
    No statistical analyses for this end point

    Secondary: Maternal length of stay in hospital

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    End point title
    Maternal length of stay in hospital
    End point description
    Details on maternal health care resource use (both for hospitalizations related to preterm labor not resulting in a delivery and hospitalizations related to preterm labor/normal labor resulting in a delivery) associated with an episode of preterm labor, preterm delivery and normal term delivery (>= 37 weeks gestation) were collected from review of medical records. Length of hospital stay associated with hospital admission for preterm labor and normal term labor/term delivery is presented. One participant in the retosiban arm did not have hospitalization data; hence, was excluded from the analysis at delivery. Only participants with data available at the specified time points were analyzed (indicated by n=X) in category titles. 99999 for dispersion indicates standard deviation could not be calculated as only one participant was analyzed. 99999 for retosiban arm indicates data was not available as the number of participants analyzed was zero.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [101]
    10 [102]
    Units: Days
    arithmetic mean (standard deviation)
        Preterm labor; n=1, 0
    2.642 ± 99999
    99999 ± 99999
        Preterm delivery; n=9, 7
    10.177 ± 11.9312
    13.583 ± 20.7670
        Normal term delivery; n=4, 2
    3.719 ± 2.2309
    4.635 ± 2.7616
    Notes
    [101] - Maternal Safety Population
    [102] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with hospital admissions related to preterm labor and preterm delivery

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    End point title
    Number of participants with hospital admissions related to preterm labor and preterm delivery
    End point description
    Maternal healthcare resource utilization associated with an episode of preterm labor and preterm delivery were collected from the review of medical records. One participant in the retosiban arm did not have hospitalization data; hence, was excluded from the analysis at delivery. The number of participants who had hospital admission for preterm labor and preterm delivery has been presented. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Up to 28 days after EDD (40 0/7 weeks of gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [103]
    10 [104]
    Units: Participants
        Preterm labor; n=13, 10
    1
    0
        Preterm delivery; n=13, 9
    9
    7
    Notes
    [103] - Maternal Safety Population
    [104] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants admitted to particular hospital unit

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    End point title
    Number of participants admitted to particular hospital unit
    End point description
    Maternal healthcare resource utilization associated with an episode of preterm labor, preterm delivery and normal term delivery were collected from the review of medical records. The number of participants who were admitted to a particular hospital unit has been presented.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [105]
    10 [106]
    Units: Participants
        General ward
    9
    2
        Private/Semi-private room
    3
    2
        Labor and delivery
    2
    3
        Labor and delivery to post-partum
    0
    1
        Post-partum
    0
    1
        Ward not specified
    0
    1
        Labor ward
    0
    1
        Antenatal ward
    0
    1
        Postnatal ward
    0
    1
    Notes
    [105] - Maternal Safety Population
    [106] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with different modes of transportation to hospital

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    End point title
    Number of participants with different modes of transportation to hospital
    End point description
    The means by which the maternal participants were transported to the hospital i.e. ground ambulance/emergency vehicle (gr. amb/emer. veh), air ambulance, family member or other means were obtained from the review of medical records. The number of maternal participants with the corresponding mode of transportation is presented for preterm labor visit and delivery visit. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles). 99999 indicates data was not available as the number of participants analyzed is zero.
    End point type
    Secondary
    End point timeframe
    Up to 28 days post EDD (40 0/7 weeks gestation)
    End point values
    Placebo Retosiban
    Number of subjects analysed
    13 [107]
    10 [108]
    Units: Participants
        Preterm labor; gr. amb/emer. veh; n=1, 0
    0
    99999
        Preterm labor; air ambulance; n=1, 0
    0
    99999
        Preterm labor; family member; n=1, 0
    1
    99999
        Preterm labor; other; n=1, 0
    0
    99999
        Delivery; gr. amb/emer. veh; n=5, 5
    2
    1
        Delivery; air ambulance; n=5, 5
    0
    0
        Delivery; family member; n=5, 5
    3
    3
        Delivery; other; n=5, 5
    0
    1
        Preterm labor;<24 hour stay;gr. amb/emer.veh;n=1,0
    0
    99999
        Preterm labor; <24 hour stay;air ambulance; n=1, 0
    0
    99999
        Preterm labor; <24 hour stay;family member; n=1, 0
    1
    99999
        Preterm labor; <24 hour stay;other; n=1, 0
    0
    99999
    Notes
    [107] - Maternal Safety Population
    [108] - Maternal Safety Population
    No statistical analyses for this end point

    Secondary: Retosiban clearance

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    End point title
    Retosiban clearance
    End point description
    Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).
    End point type
    Secondary
    End point timeframe
    Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion
    End point values
    Retosiban
    Number of subjects analysed
    10 [109]
    Units: Liters per hour
    geometric mean (geometric coefficient of variation)
        Liters per hour
    83.4 ± 5.25
    Notes
    [109] - Maternal Safety Population. Number of participants is combined from 2 studies. Actual value is 53.
    No statistical analyses for this end point

    Secondary: Volume of distribution of retosiban

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    End point title
    Volume of distribution of retosiban
    End point description
    Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).
    End point type
    Secondary
    End point timeframe
    Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion
    End point values
    Retosiban
    Number of subjects analysed
    10 [110]
    Units: Liters
    geometric mean (geometric coefficient of variation)
        Liters
    68.6 ± 109
    Notes
    [110] - Maternal Safety Population. Number of participants is combined from 2 studies. Actual value is 53.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) will be collected from the start of study treatment and until the follow up contact (Up to 6 weeks after delivery).
    Adverse event reporting additional description
    SAEs and AEs were analyzed in Maternal Safety Population and Neonatal Safety Population which comprised of mothers randomly assigned to treatment who were exposed to study treatment and neonates whose mothers received randomized treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Placebo (Maternal)
    Reporting group description
    Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, IV loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.

    Reporting group title
    Retosiban (Maternal)
    Reporting group description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period.

    Reporting group title
    Placebo (Fetal)
    Reporting group description
    Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, IV loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.

    Reporting group title
    Retosiban (Fetal)
    Reporting group description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period.

    Reporting group title
    Placebo (Neonatal)
    Reporting group description
    Placebo was 0.9 percent sodium chloride infusion matched for retosiban volume, IV loading dose over 5 minutes and continuous infusion rate including dose increase in participants with an inadequate response any time after first hour of treatment.

    Reporting group title
    Retosiban (Neonatal)
    Reporting group description
    Participants were administered 6 milligram (mg) IV loading dose of retosiban over 5 minutes followed by a 6 milligram per hour (mg/hour) continuous infusion of retosiban over 48 hours. Participants with an inadequate response any time after first hour of treatment were administered another 6 mg retosiban loading dose followed by 12 mg/hour continuous infusion for remainder of 48-hour treatment period.

    Serious adverse events
    Placebo (Maternal) Retosiban (Maternal) Placebo (Fetal) Retosiban (Fetal) Placebo (Neonatal) Retosiban (Neonatal)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    3 / 13 (23.08%)
    5 / 10 (50.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Congenital, familial and genetic disorders
    Ankyloglossia congenital
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Congenital hypothyroidism
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Neonatal respiratory distress syndrome
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Umbilical cord prolapse
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Psychiatric disorders
    Selective eating disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    2 / 10 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meconium plug syndrome
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Group B streptococcus neonatal sepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Tracheitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo (Maternal) Retosiban (Maternal) Placebo (Fetal) Retosiban (Fetal) Placebo (Neonatal) Retosiban (Neonatal)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 13 (46.15%)
    6 / 10 (60.00%)
    3 / 13 (23.08%)
    5 / 10 (50.00%)
    8 / 13 (61.54%)
    7 / 10 (70.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pregnancy, puerperium and perinatal conditions
    Oligohydramnios
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Uterine contractions abnormal
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Oedema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Granuloma
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Oedema genital
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vaccination complication
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Investigations
    Blood calcium decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Blood glucose decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Liver function test increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Body temperature fluctuation
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Cardiac disorders
    Foetal heart rate disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    5 / 10 (50.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    14
    28
    0
    0
    Foetal heart rate deceleration abnormality
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Neonatal respiratory distress syndrome
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Bronchopulmonary dysplasia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    3 / 13 (23.08%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    Pleural effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Respiratory acidosis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Tachypnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Motor dysfunction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Haematochezia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Necrotising colitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hepatobiliary disorders
    Hyperbilirubinaemia neonatal
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    6 / 13 (46.15%)
    4 / 10 (40.00%)
         occurrences all number
    0
    0
    0
    0
    6
    4
    Jaundice
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Cholestasis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pruritus generalised
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dermatitis diaper
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Dry skin
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Intertrigo
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Seborrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Osteopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Feeding intolerance
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Amniotic cavity infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Bacterial vulvovaginitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Kidney infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Device related infection
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Aug 2015
    Amendment No. 1
    14 Sep 2015
    Amendment No. 2 Revise the guidance for administration of antenatal corticosteroids to read as follows: If not previously administered, antenatal corticosteroid treatment should be administered as either (1) two 12-mg doses of betamethasone given intramuscularly 24 hours apart or (2) four 6-mg doses of dexamethasone administered intramuscularly every 12 hours. A single rescue course of antenatal corticosteroids is permitted if the antecedent treatment was at least 7 days prior to study enrollment. Clarify in the Time and Events Table (footnote 15) that hematology, chemistry, and liver function tests will only be determined through a central laboratory at the screening, Day 2, and the face-to-face post-infusion assessment visits. Incorporate other administrative changes
    19 Apr 2016
    Amendment No.3 The following changes are reflected in the Country-Specific Protocol Amendment for Italy: Amend inclusion criteria 1 and 2 to specify that participants must be at least 18 years of age to participate in Study 200719. Text was revised throughout to reflect the change in the participant age criterion. Revise text throughout to indicate that participants recruited into Study 200719 in Italy must not be dosed with the investigational product until the results of their chemical parameters have been reviewed by the Investigator and no indicators of altered liver function (AST and ALT values and bilirubinemia) are apparent. This check for altered liver function must be carried out before the study drug is administered, i.e., before initiating randomized treatment.
    20 Jun 2016
    Amendment No.4
    05 Jan 2017
    Remove screening urine drug and alcohol tests. Remove requirement that investigator confirm uterine contraction rate and cervical dilation after randomization and just before study drug administration. Add that after randomization and prior to study drug administration investigators will re-assess that tocolytic therapy is still indicated, according to their medical discretion. Clarify that an abdominal ultrasound to assess fetal growth is needed at Screening unless the most recent ultrasound is within 3 weeks (21 days) before the date of randomization. Update the list of maternal disease-related events to clarify the reporting process for events of subsequent preterm labor and hospitalization for delivery that are not worse than expected. Add that the amniotic fluid index should be measured using the 4-quadrant method. Incorporate other administrative changes.

    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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