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    Clinical Trial Results:
    A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel group, Treatment-withdrawal Study to Evaluate the Efficacy and Safety of Esomeprazole for the Treatment of Gastroesophageal Reflux Disease (GERD) in Infants Aged 1 to 11 Months, Inclusive

    Summary
    EudraCT number
    2006-005212-27
    Trial protocol
    FR   DE   Outside EU/EEA  
    Global end of trial date
    23 Sep 2008

    Results information
    Results version number
    v1(current)
    This version publication date
    18 Nov 2016
    First version publication date
    18 Nov 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D9614C00096
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca LP
    Sponsor organisation address
    1800 Concord Pike, Wilmington, Delaware, United States, 19850
    Public contact
    AZ Clinical Trial Transparency group, AstraZeneca R&D, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Gerard Lynch, AstraZeneca R&D, AZTrial_Results_Posting@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000331-PIP01-08
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Sep 2008
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Sep 2008
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Sep 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of once daily esomeprazole for reducing the esophageal and supraesophageal signs and symptoms of infantile gastroesophageal reflux disease (GERD).
    Protection of trial subjects
    The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with ICH/Good Clinical Practice and applicable regulatory requirements and the AstraZeneca policy on Bioethics.The final clinical study protocol (CSP), including the final version of the Informed Consent Form, was approved or given a favorable opinion in writing by an Ethics Committee as appropriate. The investigator submitted written approval to AstraZeneca before he or she enrolled any patient into the study. The principal investigator(s) at each center ensured that the patient’s parent/guardian was given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study. The parent/guardian was also notified that they were free to discontinue his/her child from the study at any time. The patient’s parent/guardian was given the opportunity to ask questions and allowed time to consider the information provided. The parent/guardian’s signed and dated informed consent was obtained before conducting any procedure specifically for the study. Patients could be discontinued from study treatment and assessments at any time, at the discretion of the investigator(s).
    Background therapy
    PPI within 7 days, or H2RAs or prokinetics within 24 hours prior to enrollment in the open label treatment phase were exclusion criteria.
    Evidence for comparator
    No comparator
    Actual start date of recruitment
    12 Apr 2007
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 16
    Country: Number of subjects enrolled
    Poland: 30
    Country: Number of subjects enrolled
    United States: 37
    Worldwide total number of subjects
    98
    EEA total number of subjects
    61
    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)
    98
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants aged 1 to 11 months inclusive with a clinical diagnosis of suspected Gastroesophageal Reflux Disease (GERD), symptomatic GERD, or endoscopically proven GERD enrolled First patient enrolled: 12 April 2007 Last patient completed: 4 June 2008

    Pre-assignment
    Screening details
    Of 103 patients screened for this study, 5 patients failed to be eligible. In total, 98 patients were entered into the open-label esomeprazole phase. Of these, 80 were randomized into the double-blind randomized phase.

    Period 1
    Period 1 title
    Open-label treatment phase
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Open Label Esomeprazole
    Arm description
    Open-label daily esomeprazole (2.5mg, 5mg or 10mg daily during open-label phase of the study, according to baseline weight). Eligible participants from the Open Label phase were randomized to the the double blind withdrawal phase.
    Arm type
    Experimental

    Investigational medicinal product name
    Esomeprazole magnesium
    Investigational medicinal product code
    Other name
    NEXIUM
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.5-1.3 mg/kg od orally

    Number of subjects in period 1
    Open Label Esomeprazole
    Started
    98
    Completed
    80
    Not completed
    18
         AE(5);Lack of efficacy(9); W/Consent(4)
    18
    Period 2
    Period 2 title
    Double-blind, treatment-withdrawal phase
    Is this the baseline period?
    Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double Blind Esomeprazole
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Esomeprazole magnesium
    Investigational medicinal product code
    Other name
    NEXIUM
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.5-1.3 mg/kg od orally

    Arm title
    Double Blind Placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Placebo
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.5-1.3 mg/kg od orally

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: Amongst the 98 patients who entered the open-label period 18 did not qualify to be randomized into the double-blinded period. All baseline characteristics were reported on the 80 patients randomized into the Double-Blind Randomized Period
    Number of subjects in period 2 [2]
    Double Blind Esomeprazole Double Blind Placebo
    Started
    39
    41
    Completed
    29
    24
    Not completed
    10
    17
         Lack of efficacy
    8
    17
         Adverse event, non-fatal
    2
    -
    Notes
    [2] - 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: Amongst the 98 patients who entered the open-label period 18 did not qualify to be randomized into the double-blinded period. All baseline characteristics were reported on the 80 patients randomized into the Double-Blind Randomized Period

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Double Blind Esomeprazole
    Reporting group description
    -

    Reporting group title
    Double Blind Placebo
    Reporting group description
    -

    Reporting group values
    Double Blind Esomeprazole Double Blind Placebo Total
    Number of subjects
    39 41 80
    Age categorical
    Units: Subjects
        Newborns (0-27 days)
    1 3 4
        Infants and toddlers (28 days-23 months)
    38 38 76
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    0 0 0
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age Continuous |
    Age in months
    Units: months
        arithmetic mean (standard deviation)
    4.9 ± 2.6 4.9 ± 3.2 -
    Gender, Male/Female
    Units: Participants
        Female
    9 14 23
        Male
    30 27 57
    Subject analysis sets

    Subject analysis set title
    Open label treatment phase
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Open label treatment phase

    Subject analysis set title
    Double-blind phase esomeprazole
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Double-blind phase esomeprazole

    Subject analysis set title
    Double-blind phase placebo
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Double-blind phase placebo

    Subject analysis sets values
    Open label treatment phase Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects
    98
    39
    41
    Age categorical
    Units: Subjects
        Newborns (0-27 days)
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    98
    39
    41
        Children (2-11 years)
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
        Adults (18-64 years)
    0
    0
    0
        From 65-84 years
    0
    0
    0
        85 years and over
    0
    0
    0
    Age Continuous |
    Age in months
    Units: months
        arithmetic mean (standard deviation)
    4.8 ± 2.9
    4.9 ± 2.6
    4.9 ± 3.2
    Gender, Male/Female
    Units: Participants
        Female
    35
    9
    14
        Male
    63
    30
    27

    End points

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    End points reporting groups
    Reporting group title
    Open Label Esomeprazole
    Reporting group description
    Open-label daily esomeprazole (2.5mg, 5mg or 10mg daily during open-label phase of the study, according to baseline weight). Eligible participants from the Open Label phase were randomized to the the double blind withdrawal phase.
    Reporting group title
    Double Blind Esomeprazole
    Reporting group description
    -

    Reporting group title
    Double Blind Placebo
    Reporting group description
    -

    Subject analysis set title
    Open label treatment phase
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Open label treatment phase

    Subject analysis set title
    Double-blind phase esomeprazole
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Double-blind phase esomeprazole

    Subject analysis set title
    Double-blind phase placebo
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Double-blind phase placebo

    Primary: Number of participants discontinuing due to symptom worsening in the randomized treatment withdrawal phase (Treatment withdrawal phase endpoint)

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    End point title
    Number of participants discontinuing due to symptom worsening in the randomized treatment withdrawal phase (Treatment withdrawal phase endpoint)
    End point description
    Number of participants discontinuing during the 4-week of randomized double-blind withdrawal phase that met the pre-set definition of symptom worsening criteria.
    End point type
    Primary
    End point timeframe
    Treatment-withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    39
    41
    39
    41
    Units: Participants
        Week 1
    1
    6
    1
    6
        Week 2
    7
    6
    7
    6
        Week 3
    2
    1
    2
    1
        Week 4
    5
    7
    5
    7
    Statistical analysis title
    Analysis of time to discontinuation
    Statistical analysis description
    Analysis of time to discontinuation due to symptom worsening.
    Comparison groups
    Double Blind Esomeprazole v Double Blind Placebo v Double-blind phase esomeprazole v Double-blind phase placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2751
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.35
         upper limit
    1.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4

    Secondary: Number of participants discontinuing due to any reason, including symptom worsening, in the randomized treatment withdrawal phase (Treatment withdrawal phase endpoint)

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    End point title
    Number of participants discontinuing due to any reason, including symptom worsening, in the randomized treatment withdrawal phase (Treatment withdrawal phase endpoint)
    End point description
    Number of participants discontinuing due to any reason was identical to the number of participants discontinuing due to symptom worsening (the primary assessment) when no participants discontinued due to reason other than symptom worsening.
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    39
    41
    39
    41
    Units: Participants
        Week 1
    1
    6
    1
    6
        Week 2
    7
    6
    7
    6
        Week 3
    2
    1
    2
    1
        Week 4
    5
    7
    5
    7
    Statistical analysis title
    Time to discontinuation due to any reason
    Comparison groups
    Double Blind Esomeprazole v Double Blind Placebo v Double-blind phase esomeprazole v Double-blind phase placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2751
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.35
         upper limit
    1.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4

    Secondary: Treatment successes at the end of the 4-week double-blind treatment withdrawal phase (Treatment withdrawal phase endpoint).

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    End point title
    Treatment successes at the end of the 4-week double-blind treatment withdrawal phase (Treatment withdrawal phase endpoint).
    End point description
    The number of participants reaching the end of the treatment withdrawal phase without discontinuing from the study (for any reason) or showing symptom worsening in the physician global assessment of Gastroesophageal Reflux Disease (GERD) symptoms. Based on the severity of symptoms reported by the parent/guardian in IVRS, the investigator provided the overall clinical impression of the patient’s GERD-related symptoms over the last 7 days as: None Mild Moderate Severe
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    39
    41
    39
    41
    Units: Participants
    24
    21
    24
    21
    Statistical analysis title
    Analysis of the number of responders
    Statistical analysis description
    Analysis of the number of treatment responders at the end of the double-blind phase
    Comparison groups
    Double Blind Esomeprazole v Double Blind Placebo v Double-blind phase esomeprazole v Double-blind phase placebo
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3524
    Method
    Chi-squared
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.524
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.626
         upper limit
    3.709
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.45

    Secondary: Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) symptoms (Treatment withdrawal phase endpoint)

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    End point title
    Physician's Global Assessment (PGA) of Gastroesophageal Reflux Disease (GERD) symptoms (Treatment withdrawal phase endpoint)
    End point description
    Percentage of participants with Physician's Global Assessment (PGA) score at the final treatment withdrawal assessment in following categories: None (no symptoms), Mild, Moderate or Severe. The worst post-randomization Physician's Global Assessment (PGA) assessment during double blind phase is taken into account.
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study)
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    39
    41
    39
    41
    Units: Percentage of participants
    number (not applicable)
        None
    0
    0
    0
    0
        Mild
    2.6
    7.3
    2.6
    7.3
        Moderate
    76.9
    78
    76.9
    78
        Severe
    20.5
    14.6
    20.5
    14.6
    No statistical analyses for this end point

    Secondary: Severity of Vomiting/regurgitation symptoms as reported by the parent/guardian (Treatment withdrawal phase endpoint)

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    End point title
    Severity of Vomiting/regurgitation symptoms as reported by the parent/guardian (Treatment withdrawal phase endpoint)
    End point description
    Change from baseline in symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    37
    40
    37
    40
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.04 ± 0.56
    0.09 ± 0.61
    0.04 ± 0.56
    0.09 ± 0.61
    No statistical analyses for this end point

    Secondary: Severity of irritability crying/fussing symptoms as reported by the parent/guardian (Treatment withdrawal phase endpoint)

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    End point title
    Severity of irritability crying/fussing symptoms as reported by the parent/guardian (Treatment withdrawal phase endpoint)
    End point description
    Change from baseline in symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    37
    40
    37
    40
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.06 ± 0.58
    0.19 ± 0.59
    0.06 ± 0.58
    0.19 ± 0.59
    No statistical analyses for this end point

    Secondary: Severity of supraesophageal/respiratory disturbances (coughing/wheezing,labored breathing) as reported by parent/guardian (Treatment withdrawal phase endpoint)

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    End point title
    Severity of supraesophageal/respiratory disturbances (coughing/wheezing,labored breathing) as reported by parent/guardian (Treatment withdrawal phase endpoint)
    End point description
    Change from baseline in symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    37
    40
    37
    40
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.12 ± 0.48
    0.03 ± 0.58
    0.12 ± 0.48
    0.03 ± 0.58
    No statistical analyses for this end point

    Secondary: Severity of feeding difficulties reported by parent/guardian (Treatment withdrawal phase endpoint)

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    End point title
    Severity of feeding difficulties reported by parent/guardian (Treatment withdrawal phase endpoint)
    End point description
    Change from baseline in symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, final severity score is the mean severity in the final 7-days, while baseline is the mean severity in the 7-day period up to and including randomization. Changes less than zero indicate improved severity versus baseline. Participants needed baseline measure and one additional post baseline measure to be included in analysis.
    End point type
    Secondary
    End point timeframe
    Treatment withdrawal phase (up to 4 weeks following randomization, or until earlier discontinuation from the study) Change was calculated from baseline to last measure obtained
    End point values
    Double Blind Esomeprazole Double Blind Placebo Double-blind phase esomeprazole Double-blind phase placebo
    Number of subjects analysed
    37
    40
    37
    40
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.09 ± 0.48
    0.1 ± 0.61
    0.09 ± 0.48
    0.1 ± 0.61
    No statistical analyses for this end point

    Secondary: Improvement in Physician's Global Assessment (PGA) following open-label esomeprazole (Open-label phase endpoint)

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    End point title
    Improvement in Physician's Global Assessment (PGA) following open-label esomeprazole (Open-label phase endpoint)
    End point description
    Number of patients who had an improvement of at least one category in the PGA at the end of open-label treatment with esomeprazole compared to baseline. Improvement in PGA was a pre-requisite for randomization into the randomized treatment withdrawal phase. Only patients with PGA at baseline and end of open-label are analyzed here.
    End point type
    Secondary
    End point timeframe
    Open-label treatment period (2 weeks)
    End point values
    Open Label Esomeprazole Open label treatment phase
    Number of subjects analysed
    98
    98
    Units: Participants
    81
    81
    No statistical analyses for this end point

    Secondary: Severity of Vomiting/regurgitation symptoms as reported by the parent/guardian (Open-label phase)

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    End point title
    Severity of Vomiting/regurgitation symptoms as reported by the parent/guardian (Open-label phase)
    End point description
    Symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, The score is the mean severity in each 7-day period.
    End point type
    Secondary
    End point timeframe
    Open Label phase (Screening plus two weeks)
    End point values
    Open Label Esomeprazole Open label treatment phase
    Number of subjects analysed
    98
    98
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Screening
    1.42 ± 0.76
    1.42 ± 0.76
        Week 1
    1.14 ± 0.67
    1.14 ± 0.67
        Week 2
    1 ± 0.72
    1 ± 0.72
    No statistical analyses for this end point

    Secondary: Severity of irritability crying/fussing symptoms as reported by the parent/guardian (Open-label phase endpoint)

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    End point title
    Severity of irritability crying/fussing symptoms as reported by the parent/guardian (Open-label phase endpoint)
    End point description
    Symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, The score is the mean severity in each 7-day period.
    End point type
    Secondary
    End point timeframe
    Open Label Phase (Screening plus two weeks)
    End point values
    Open Label Esomeprazole Open label treatment phase
    Number of subjects analysed
    98
    98
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Screening
    1.5 ± 0.67
    1.5 ± 0.67
        Week 1
    1.22 ± 0.68
    1.22 ± 0.68
        Week 2
    1.02 ± 0.74
    1.02 ± 0.74
    No statistical analyses for this end point

    Secondary: Severity of supraesophageal/respiratory disturbances (coughing/wheezing,labored breathing) as reported by parent/guardian (Open-label phase endpoint)

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    End point title
    Severity of supraesophageal/respiratory disturbances (coughing/wheezing,labored breathing) as reported by parent/guardian (Open-label phase endpoint)
    End point description
    Symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, The score is the mean severity in each 7-day period.
    End point type
    Secondary
    End point timeframe
    Open Label Phase (Screening plus two weeks)
    End point values
    Open Label Esomeprazole Open label treatment phase
    Number of subjects analysed
    98
    98
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Screening
    0.54 ± 0.69
    0.54 ± 0.69
        Week 1
    0.48 ± 0.61
    0.48 ± 0.61
        Week 2
    0.44 ± 0.69
    0.44 ± 0.69
    No statistical analyses for this end point

    Secondary: Severity of feeding difficulties as reported by parent/guardian (Open-label phase endpoint)

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    End point title
    Severity of feeding difficulties as reported by parent/guardian (Open-label phase endpoint)
    End point description
    Symptom severity (Severity is scored as 0-4 [none, mild moderate, severe]). For each participant, The score is the mean severity in each 7-day period.
    End point type
    Secondary
    End point timeframe
    Open Label Phase (Screening plus two weeks)
    End point values
    Open Label Esomeprazole Open label treatment phase
    Number of subjects analysed
    98
    98
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Screening
    1.16 ± 0.76
    1.16 ± 0.76
        Week 1
    0.94 ± 0.71
    0.94 ± 0.71
        Week 2
    0.83 ± 0.76
    0.83 ± 0.76
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    During openlabel phase 2 weeks and doubleblind randomised treatment 4 weeks.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    Open-label phase
    Reporting group description
    Open-label daily esomeprazole (2.5mg, 5mg or 10mg daily during open-label phase of the study, according to baseline weight).

    Reporting group title
    Double Blind Esomeprazole
    Reporting group description
    Eligible participants from the Open Label phase were randomized to the the double blind withdrawal phase.

    Reporting group title
    Double Blind Placebo
    Reporting group description
    Eligible participants from the Open Label phase were randomized to the the double blind withdrawal phase.

    Serious adverse events
    Open-label phase Double Blind Esomeprazole Double Blind Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 98 (4.08%)
    3 / 39 (7.69%)
    0 / 41 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Poor Peripheral Circulation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 39 (2.56%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Apnoea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 39 (2.56%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 39 (2.56%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure To Thrive
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 39 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Chlamydial Infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    1 / 39 (2.56%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Bronchiolitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 39 (2.56%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotavirus Infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 39 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 39 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Open-label phase Double Blind Esomeprazole Double Blind Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 98 (47.96%)
    23 / 39 (58.97%)
    27 / 41 (65.85%)
    Respiratory, thoracic and mediastinal disorders
    Cough
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 98 (3.06%)
    3 / 39 (7.69%)
    4 / 41 (9.76%)
         occurrences all number
    47
    23
    27
    Pharyngolaryngeal Pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 98 (0.00%)
    2 / 39 (5.13%)
    0 / 41 (0.00%)
         occurrences all number
    47
    23
    27
    General disorders and administration site conditions
    Pyrexia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 98 (4.08%)
    5 / 39 (12.82%)
    3 / 41 (7.32%)
         occurrences all number
    47
    23
    27
    Gastrointestinal disorders
    Constipation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    1 / 39 (2.56%)
    4 / 41 (9.76%)
         occurrences all number
    47
    23
    27
    Diarrhoea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 98 (3.06%)
    4 / 39 (10.26%)
    2 / 41 (4.88%)
         occurrences all number
    47
    23
    27
    Flatulence
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    2 / 39 (5.13%)
    1 / 41 (2.44%)
         occurrences all number
    47
    23
    27
    Teething
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 98 (4.08%)
    3 / 39 (7.69%)
    2 / 41 (4.88%)
         occurrences all number
    47
    23
    27
    Vomiting
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 39 (5.13%)
    2 / 41 (4.88%)
         occurrences all number
    47
    23
    27
    Skin and subcutaneous tissue disorders
    Rash
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 98 (1.02%)
    2 / 39 (5.13%)
    1 / 41 (2.44%)
         occurrences all number
    47
    23
    27
    Infections and infestations
    Bronchitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 98 (4.08%)
    3 / 39 (7.69%)
    2 / 41 (4.88%)
         occurrences all number
    47
    23
    27
    Nasopharyngitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 98 (2.04%)
    4 / 39 (10.26%)
    3 / 41 (7.32%)
         occurrences all number
    47
    23
    27
    Otitis Media
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 39 (5.13%)
    1 / 41 (2.44%)
         occurrences all number
    47
    23
    27
    Rhinitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 98 (3.06%)
    4 / 39 (10.26%)
    3 / 41 (7.32%)
         occurrences all number
    47
    23
    27
    Upper Respiratory Tract Infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 98 (5.10%)
    6 / 39 (15.38%)
    4 / 41 (9.76%)
         occurrences all number
    47
    23
    27
    Ear Infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 98 (0.00%)
    2 / 39 (5.13%)
    1 / 41 (2.44%)
         occurrences all number
    47
    23
    27

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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