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    Clinical Trial Results:
    A two part, double-blind, randomized, placebo-controlled and open-label study to investigate the efficacy, safety and tolerability of eltrombopag, a thrombopoietin receptor agonist, in pediatric patients with previously treated chronic immune (idiopathic) thrombocytopenic purpura (ITP).

    Summary
    EudraCT number
    2011-002184-17
    Trial protocol
    CZ   DE   ES   GB   PL   IT  
    Global end of trial date
    02 Jan 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Mar 2016
    First version publication date
    08 Mar 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    TRA115450
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01520909
    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 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Feb 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Jan 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jan 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of eltrombopag, relative to placebo, in achieving platelet counts of >= 50 Gi/L, when administered to pediatric subjects with previously treated chronic ITP during the first 12 weeks of Part 1, the randomized treatment period.
    Protection of trial subjects
    Liver stopping criteria – in the instance that liver tests indicate elevated levels, the criteria will advise how to monitor patients as well as study procedure interruption or discontinuation. Dosing Guidelines – guidelines are put into place to ensure, based on individual platelet response, study treatment will maintain platelet counts in a safe hemostatic range, not necessarily in the normal range.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Feb 2012
    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
    Spain: 3
    Country: Number of subjects enrolled
    Taiwan: 2
    Country: Number of subjects enrolled
    Thailand: 25
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    United States: 4
    Country: Number of subjects enrolled
    Argentina: 4
    Country: Number of subjects enrolled
    China: 2
    Country: Number of subjects enrolled
    Czech Republic: 7
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Russian Federation: 13
    Worldwide total number of subjects
    92
    EEA total number of subjects
    34
    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)
    1
    Children (2-11 years)
    57
    Adolescents (12-17 years)
    34
    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
    Pediatric participants meeting eligibility criteria were enrolled into 3 cohorts depending upon age. Cohort 1 enrolled participants who were between 12 and 17 years old, Cohort 2 enrolled participants who were between 6 and 11 years old, and Cohort 3 enrolled participants who were between 1 and 5 years old.

    Pre-assignment
    Screening details
    This study was comprised of a 13-week Double-Blind (DB), randomized Treatment Period (Part 1), followed by a 24-week Open-Label (OL) eltrombopag-only period (Part 2). After completion of Part 2, participants completed a 24- to 28-week Follow-up period, including an ophthalmic examination 24 weeks after the last dose of study treatment.

    Period 1
    Period 1 title
    Part 1 (Randomized Period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part 1 (Randomized Period)-Placebo
    Arm description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kilograms (kg) received placebo 37.5 milligrams (mg) once daily (QD), and those with a body weight >=27 kg received placebo 50 mg QD. Participants of East Asian ancestry received a starting dose of placebo 25 mg QD. Participants aged between 1 and 5 years received placebo 1.2 milligrams per kilogram (mg/kg) QD; participants of East Asian ancestry received a starting dose of placebo 0.8 milligrams per kilograms per day (mg/kg/day). Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo to match eltrombopag 12.5mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Placebo to match eltrombopag 25, 50, 75mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg

    Investigational medicinal product name
    Placebo to match eltrombopag 20mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Powder for oral suspension is combined with 9.5mL of water and drawn into a 10cc oral syringe for oral administration once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Arm title
    Part 1 (Randomized Period)-Eltrombopag
    Arm description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD. Participants aged between 1 and 5 years received eltrombopag 1.2 mg/kg QD; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day. Participants continued on the same dose of eltrombopag in Part 2 unless adjustments were warranted according to the dosing guidelines. Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.
    Arm type
    Active comparator

    Investigational medicinal product name
    Eltrombopag 12.5mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 25mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 50mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 75mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 20mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Powder for oral suspension is combined with 9.5mL of water and drawn into a 10cc oral syringe for oral administration once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Number of subjects in period 1
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Started
    29
    63
    Completed
    28
    61
    Not completed
    1
    2
         Adverse event, non-fatal
    1
    2
    Period 2
    Period 2 title
    Part 2 Open-Label Period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Part 2 (Open-Label Period) - Eltrombopag
    Arm description
    All participants receiving placebo in Part 1 received eltrombopag in Part 2 following starting dose guidelines for Part 1. Participants aged between 6 and 17 years with a body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD. Participants aged between 1 and 5 years received eltrombopag 1.2 mg/kg QD; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day. Participants receving eltrombopag in Part 1 continued on the same dose of eltrombopag in Part 2 unless adjustments were warranted according to the dosing guidelines. Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Eltrombopag 12.5mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 25mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 50mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 75mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Investigational medicinal product name
    Eltrombopag 20mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Powder for oral suspension is combined with 9.5mL of water and drawn into a 10cc oral syringe for oral administration once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

    Number of subjects in period 2 [1]
    Part 2 (Open-Label Period) - Eltrombopag
    Started
    87
    Completed
    80
    Not completed
    7
         Withdrawal by parent/guardian
    1
         Lack of efficacy
    2
         Adverse event, non-fatal
    4
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Two participants completed Part 1: Randomized Period but did not endter Part 2: Open-Label Period because the participants withdrew consent.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1 (Randomized Period)-Placebo
    Reporting group description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kilograms (kg) received placebo 37.5 milligrams (mg) once daily (QD), and those with a body weight >=27 kg received placebo 50 mg QD. Participants of East Asian ancestry received a starting dose of placebo 25 mg QD. Participants aged between 1 and 5 years received placebo 1.2 milligrams per kilogram (mg/kg) QD; participants of East Asian ancestry received a starting dose of placebo 0.8 milligrams per kilograms per day (mg/kg/day). Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.

    Reporting group title
    Part 1 (Randomized Period)-Eltrombopag
    Reporting group description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD. Participants aged between 1 and 5 years received eltrombopag 1.2 mg/kg QD; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day. Participants continued on the same dose of eltrombopag in Part 2 unless adjustments were warranted according to the dosing guidelines. Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.

    Reporting group values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag Total
    Number of subjects
    29 63 92
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Infants and toddlers (28 days-23 months)
    0
        Newborns (0-27 days)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    9.8 ± 4 9.4 ± 4.43 -
    Gender categorical
    Units: Subjects
        Female
    14 30 44
        Male
    15 33 48
    Race
    Units: Subjects
        African American/African Heritage
    0 1 1
        Central/South Asian Heritage
    0 1 1
        Japanese/East Asian/South East Asian Heritage
    10 20 30
        Arabic/North African Heritage
    1 2 3
        White/Caucasian/European Heritage
    18 38 56
        Mixed Race
    0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Part 1 (Randomized Period)-Placebo
    Reporting group description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kilograms (kg) received placebo 37.5 milligrams (mg) once daily (QD), and those with a body weight >=27 kg received placebo 50 mg QD. Participants of East Asian ancestry received a starting dose of placebo 25 mg QD. Participants aged between 1 and 5 years received placebo 1.2 milligrams per kilogram (mg/kg) QD; participants of East Asian ancestry received a starting dose of placebo 0.8 milligrams per kilograms per day (mg/kg/day). Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.

    Reporting group title
    Part 1 (Randomized Period)-Eltrombopag
    Reporting group description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD. Participants aged between 1 and 5 years received eltrombopag 1.2 mg/kg QD; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day. Participants continued on the same dose of eltrombopag in Part 2 unless adjustments were warranted according to the dosing guidelines. Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.
    Reporting group title
    Part 2 (Open-Label Period) - Eltrombopag
    Reporting group description
    All participants receiving placebo in Part 1 received eltrombopag in Part 2 following starting dose guidelines for Part 1. Participants aged between 6 and 17 years with a body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD. Participants aged between 1 and 5 years received eltrombopag 1.2 mg/kg QD; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day. Participants receving eltrombopag in Part 1 continued on the same dose of eltrombopag in Part 2 unless adjustments were warranted according to the dosing guidelines. Standard of care treatments were allowed during the study, and were prescribed based on the investigator's discretion.

    Subject analysis set title
    Eltrombopag Cohort 1 (12-17 years)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received eltrombopag in Part 1 continued on the same dose in Part 2 unless adjustments were warranted according to the dosing guidelines. Participants who received placebo in Part 1 received Eltrombopag as per age criteria as follows:body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD.

    Subject analysis set title
    Eltrombopag Cohort 2 (6-11 years)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received eltrombopag in Part 1 continued on the same dose in Part 2 unless adjustments were warranted according to the dosing guidelines. Participants who received placebo in Part 1 received Eltrombopag as per age criteria as follows: body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD.

    Subject analysis set title
    Eltrombopag Cohort 3 (1-5 years)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received eltrombopag in Part 1 continued on the same dose in Part 2 unless adjustments were warranted according to the dosing guidelines. Participants who received placebo in Part 1 received Eltrombopag 1.2 mg/kg QD and; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day.

    Primary: Number of participants achieving a platelet count >=50 giga cells per liter (Gi/L) for at least 6 out of 8 weeks, between Weeks 5 and 12 of Part 1

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    End point title
    Number of participants achieving a platelet count >=50 giga cells per liter (Gi/L) for at least 6 out of 8 weeks, between Weeks 5 and 12 of Part 1
    End point description
    Participants who achieved a platelet count >=50 Gi/L for at least 6 out of 8 weeks, between Weeks 5 and 12 of Part 1, were reported.
    End point type
    Primary
    End point timeframe
    From Week 5 up to Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [1]
    63 [2]
    Units: Participants
    1
    25
    Notes
    [1] - Intent-to-Treat (ITT) Population
    [2] - Intent-to-Treat (ITT) Population
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    The proportion of participants achieving platelet counts >=50 Gi/L for those participants receiving eltrombopag versus placebo was compared.
    Comparison groups
    Part 1 (Randomized Period)-Eltrombopag v Part 1 (Randomized Period)-Placebo
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001 [3]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    17.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.29
         upper limit
    140.93
    Notes
    [3] - Indicated significance at the 5% (two-sided) level of significance

    Secondary: Percentage of Responders

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    End point title
    Percentage of Responders
    End point description
    Percentage of participants who responded (defined as platelet count >= 50Gi/L in absence of rescue) at least once up to week 12 of Part 1 (Odds of achieving a platelet count >=50 Gi/L during the first 12 weeks of Part 1)
    End point type
    Secondary
    End point timeframe
    From Week 1 up to Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [4]
    63 [5]
    Units: Percentage of Participants
    number (not applicable)
        Week 1
    0
    15.9
        Week 2
    3.4
    23.8
        Week 3
    0
    31.7
        Week 4
    6.9
    36.5
        Week 5
    6.9
    47.6
        Week 6
    6.9
    38.1
        Week 7
    10.3
    44.4
        Week 8
    3.4
    44.4
        Week 9
    3.4
    42.9
        Week 10
    3.4
    52.4
        Week 11
    6.9
    49.2
        Week 12
    3.4
    58.7
    Notes
    [4] - ITT population
    [5] - ITT population
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Part 1 (Randomized Period)-Placebo v Part 1 (Randomized Period)-Eltrombopag
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001 [6]
    Method
    Repeated Measures model for binary data
    Parameter type
    Odds ratio (OR)
    Point estimate
    25.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.15
         upper limit
    78.73
    Notes
    [6] - Repeated measures model for binary data using Generalized linear mixed model.

    Secondary: Number of participants achieving a platelet count >=50 Gi/L at any time during the first 12 weeks of Part 1

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    End point title
    Number of participants achieving a platelet count >=50 Gi/L at any time during the first 12 weeks of Part 1
    End point description
    Participants who achieved a platelet count >=50 Gi/L at any time during the first 12 weeks of Part 1 were reported.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [7]
    63 [8]
    Units: Participants
    6
    47
    Notes
    [7] - ITT population
    [8] - ITT population
    No statistical analyses for this end point

    Secondary: Number of participants achieving a platelet count >=50 Gi/L at any time during the first 6 weeks of Part 1

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    End point title
    Number of participants achieving a platelet count >=50 Gi/L at any time during the first 6 weeks of Part 1
    End point description
    Participants who achieved a platelet count >=50 Gi/L at any time during the first 6 weeks of Part 1 were reported.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 6 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [9]
    63 [10]
    Units: Participants
    5
    39
    Notes
    [9] - ITT population
    [10] - ITT population
    No statistical analyses for this end point

    Secondary: Weighted mean platelet count

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    End point title
    Weighted mean platelet count
    End point description
    The weighted mean platelet count is defined as "the area under the platelet-time curve divided by the duration of the study (12 weeks)". Weighted mean platelet counts from baseline to week 12 of the randomized period was compared between placebo and eltrombopag using an analysis of covariance model (ANCOVA) adjusting for baseline platelet count and age cohort. For each subject the area between two adjacent visits with platelet counts was calculated. The area was calculated for all pairs of adjacent visits starting at Day 1 of randomized period and then the total sum of all the areas was divided by the total duration of time during the randomized period. For each subject, this method calculates an ‘average’ platelet count and it allows the possibility that subjects may have had different number of assessments during different times relative to baseline.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [11]
    62 [12]
    Units: Gi/L
    arithmetic mean (standard deviation)
        Baseline
    14.2 ± 8.01
    14 ± 8.09
        Week 12
    23.7 ± 19.56
    63.9 ± 46.68
    Notes
    [11] - ITT Population. Only those participants with a value at Baseline and post-Baseline were analyzed
    [12] - ITT Population. Only those participants with a value at Baseline and post-Baseline were analyzed
    No statistical analyses for this end point

    Secondary: Maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L during the first 12 weeks of Part 1

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    End point title
    Maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L during the first 12 weeks of Part 1
    End point description
    The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L was calculated and summarized for the first 12 weeks of Part 1. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If a particpant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [13]
    63 [14]
    Units: Weeks
        arithmetic mean (standard deviation)
    0.4 ± 1.5
    3.3 ± 3.13
    Notes
    [13] - ITT population
    [14] - ITT population
    No statistical analyses for this end point

    Secondary: Number of participants who required a protocol-defined rescue treatment during Part 1

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    End point title
    Number of participants who required a protocol-defined rescue treatment during Part 1
    End point description
    Rescue treatment is defined as either a new immune (idiopathic) thrombocytopenic purpura (ITP) medication, an increase in the dose of a concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [15]
    63 [16]
    Units: Participants
        number (not applicable)
    7
    12
    Notes
    [15] - ITT population
    [16] - ITT population
    No statistical analyses for this end point

    Secondary: Number of participants with any bleeding and significant bleeding as assessed using the World Health Organization (WHO) Bleeding Scale during Part 1

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    End point title
    Number of participants with any bleeding and significant bleeding as assessed using the World Health Organization (WHO) Bleeding Scale during Part 1
    End point description
    The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross bleeding; Grade 4=debilitating blood loss. The WHO grades were dichotomized into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. Baseline was defined as the Day 1 assessment or the latest possible screening assessment. Only those participants that did not enroll in Part 2 were analyzed during the follow-up visits. Only those participants available at the specified time points were analyzed (represented by n=X,X in the category titles).
    End point type
    Secondary
    End point timeframe
    From Baseline through Follow-up of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [17]
    63 [18]
    Units: Participants
    number (not applicable)
        Baseline, Any bleeding n=29,63
    20
    45
        Baseline, Significant bleeding n=29,63
    6
    16
        Week 1, Any bleeding n=29,63
    19
    41
        Week 1, Significant bleeding n=29,63
    3
    8
        Week 2, Any bleeding n=29,63
    19
    33
        Week 2, Significant bleeding n=29,63
    6
    6
        Week 3, Any bleeding n=28,62
    18
    32
        Week 3, Significant bleeding n=28,62
    3
    7
        Week 4, Any bleeding n=29, 62
    20
    27
        Week 4, Significant bleeding n=29, 62
    4
    4
        Week 5, Any bleeding n=27, 62
    18
    22
        Week 5, Significant bleeding n=27, 62
    2
    5
        Week 6, Any bleeding n=28, 62
    17
    24
        Week 6, Significant bleeding n=28, 62
    0
    5
        Week 7, Any bleeding n=28, 63
    14
    20
        Week 7, Significant bleeding n=28, 63
    1
    1
        Week 8, Any bleeding n=28, 63
    17
    24
        Week 8,Significant bleeding n=28, 63
    1
    4
        Week 9, Any bleeding n=27, 61
    18
    24
        Week 9, Significant bleeding n=27, 61
    3
    4
        Week 10, Any bleeding n=28, 62
    17
    20
        Week 10, Significant bleeding n=28, 62
    2
    4
        Week 11, Any bleeding n=28, 61
    16
    26
        Week 11, Significant bleeding n=28, 61
    3
    8
        Week 12, Any bleeding n=28, 61
    16
    23
        Week 12, Significant bleeding n=28, 61
    2
    3
        Follow-up Week 1, Any bleeding n=0,2
    0
    1
        Follow-up Week 1, Significant bleeding n=0,2
    0
    0
        Follow-up Week 2, Any bleeding n=0,2
    0
    1
        Follow-up Week 2, Significant bleeding n=0,2
    0
    0
        Follow-up Week 3, Any bleeding n=0,3
    0
    2
        Follow-up Week 3, Significant bleeding n=0,3
    0
    1
        Follow-up Week 4, Any bleeding n=0,1
    0
    1
        Follow-up Week 4, Significant bleeding n=0,1
    0
    1
        Any follow-up Week, Any bleeding n=0,3
    0
    2
        Any Follow-up Week, Significant bleeding n=0,3
    0
    1
    Notes
    [17] - ITT population
    [18] - ITT population
    No statistical analyses for this end point

    Secondary: Number of participants who achieved a platelet count >=50 Gi/L at any time during Part 2

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    End point title
    Number of participants who achieved a platelet count >=50 Gi/L at any time during Part 2
    End point description
    Participants who achieved a platelet count >=50 Gi/L at any time during Part 2 (up to Week 24) were reported.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [19]
    Units: Participants
        number (not applicable)
    70
    Notes
    [19] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed
    No statistical analyses for this end point

    Secondary: Number of weeks in which participants achieved a platelet count >=50 Gi/L, between Weeks 4 and 24 of Part 2

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    End point title
    Number of weeks in which participants achieved a platelet count >=50 Gi/L, between Weeks 4 and 24 of Part 2
    End point description
    Platelet response was analyzed after Week 4 for the eltrombopag-only period to allow participants who had been randomized to placebo in the Randomized Period time to escalate to their optimal dose of eltrombopag. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If the participant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.
    End point type
    Secondary
    End point timeframe
    From Week 4 up to Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [20]
    Units: Weeks
        arithmetic mean (standard deviation)
    10 ± 7.67
    Notes
    [20] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed
    No statistical analyses for this end point

    Secondary: Maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L during Part 2

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    End point title
    Maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L during Part 2
    End point description
    The maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L was calculated and summarized for the 24 weeks of eltrombopag dosing (Part 2). Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If the participant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [21]
    Units: Weeks
        arithmetic mean (standard deviation)
    8.6 ± 7.84
    Notes
    [21] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed
    No statistical analyses for this end point

    Secondary: Number of participants who reduced or discontinued Baseline concomitant ITP medications during Part 2 without requiring subsequent rescue therapy

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    End point title
    Number of participants who reduced or discontinued Baseline concomitant ITP medications during Part 2 without requiring subsequent rescue therapy
    End point description
    Participants who discontinued or had a sustained reduction of a baseline immune (idiopathic) thrombocytopenic purpura (ITP) medication during the 24 weeks of Part 2 (Open-Label Period) and without requiring subsequent rescue therapy. For participants randomized to placebo in Part 1, Baseline is defined as Week 13 of Part 1. For participants randomized to eltrombopag in Part 1, Baseline is defined as Day 1 of Part 1. A sustained reduction was defined as a reduction for 4 weeks or more. Only those participants who entered into Part 2 (Open-label eltrombopag-only phase) and taking an ITP medication at Baseline were analyzed.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    15 [22]
    Units: Participants
        number (not applicable)
    8
    Notes
    [22] - ITT population
    No statistical analyses for this end point

    Secondary: Number of participants who required a protocol-defined rescue treatment during Part 2

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    End point title
    Number of participants who required a protocol-defined rescue treatment during Part 2
    End point description
    Rescue treatment was defined as either a new immune (idiopathic) thrombocytopenic purpura (ITP) medication, an increase in the dose of a concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [23]
    Units: Participants
        number (not applicable)
    11
    Notes
    [23] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed
    No statistical analyses for this end point

    Secondary: Number of participants with any bleeding and significant bleeding as assessed using the WHO Bleeding Scale during Part 2

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    End point title
    Number of participants with any bleeding and significant bleeding as assessed using the WHO Bleeding Scale during Part 2
    End point description
    The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0 = no bleeding, Grade 1 = petechiae, Grade 2 = mild blood loss, Grade 3 = gross bleeding and Grade 4 = debilitating blood loss. The WHO Grades were dichotomized into the following categories: no bleeding = Grade 0; any bleeding = Grade 1 to 4; no clinically significant bleeding = Grade 0 to 1; clinically significant bleeding = Grade 2 to 4. Only those participants who entered into Part 2 open-label Eltrombopag only phase were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    From Baseline of Part 2 through Follow-up
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [24]
    Units: Participants
    number (not applicable)
        Baseline, Any bleeding n=87
    55
        Baseline, Significant bleeding n=87
    17
        Week 1, Any bleeding n=86
    29
        Week 1, Significant bleeding n=86
    3
        Week 2, Any bleeding n=85
    22
        Week 2, Significant bleeding n=85
    2
        Week 3, Any bleeding n=86
    20
        Week 3, Significant bleeding n=86
    1
        Week 4, Any bleeding n=68
    20
        Week 4, Significant bleeding n=68
    4
        Week 5, Any bleeding n=61
    21
        Week 5, Significant bleeding n=61
    4
        Week 6, Any bleeding n=55
    17
        Week 6, Significant bleeding n=55
    3
        Week 7, Any bleeding n=52
    14
        Week 7, Significant bleeding n=52
    1
        Week 8, Any bleeding n=52
    17
        Week 8, Significant bleeding n=52
    4
        Week 9, Any bleeding n=45
    11
        Week 9, Significant bleeding n=45
    1
        Week 10, Any bleeding n=42
    8
        Week 10, Significant bleeding n=42
    2
        Week 11, Any bleeding n=40
    12
        Week 11, Significant bleeding n=40
    3
        Week 12, Any bleeding n=63
    15
        Week 12, Significant bleeding n=63
    5
        Week 13, Any bleeding n=30
    9
        Week 13, Significant bleeding n=30
    2
        Week 14, Any bleeding n=38
    9
        Week 14, Significant bleeding n=38
    2
        Week 15, Any bleeding n=43
    10
        Week 15, Significant bleeding n=43
    2
        Week 16, Any bleeding n=47
    11
        Week 16, Significant bleeding n=47
    4
        Week 17, Any bleeding n=37
    10
        Week 17, Significant bleeding n=37
    2
        Week 18, Any bleeding n=33
    8
        Week 18, Significant bleeding n=33
    1
        Week 19, Any bleeding n=44
    15
        Week 19, Significant bleeding n=44
    2
        Week 20, Any bleeding n=39
    7
        Week 20, Significant bleeding n=39
    2
        Week 21, Any bleeding n=41
    10
        Week 21, Significant bleeding n=41
    2
        Week 22, Any bleeding n=34
    7
        Week 22, Significant bleeding n=34
    3
        Week 23, Any bleeding n=36
    15
        Week 23, Significant bleeding n=36
    2
        Week 24, Any bleeding n=79
    19
        Week 24, Significant bleeding n=79
    5
        Follow-up Week 1, Any bleeding n=29
    8
        Follow-up Week 1, Significant bleeding n=29
    2
        Follow-up Week 2, Any bleeding n=37
    25
        Follow-up Week 2, Significant bleeding n=37
    5
        Follow-up Week 3, Any bleeding n=40
    17
        Follow-up Week 3, Significant bleeding n=40
    5
        Follow-up Week 4, Any bleeding n=70
    23
        Follow-up Week 4, Significant bleeding n=70
    3
        Any follow-up Week, Any bleeding n=77
    38
        Any Follow-up Week, Significant bleeding n=77
    8
    Notes
    [24] - ITT population
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse event (AE) or serious adverse event (SAE) during Part 1

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    End point title
    Number of participants with any adverse event (AE) or serious adverse event (SAE) during Part 1
    End point description
    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (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 or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Treatment up to Week 13 of Part 1+ 1 day
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [25]
    63 [26]
    Units: Participants
    number (not applicable)
        Any AE
    21
    51
        Any SAE
    4
    5
    Notes
    [25] - Safety Population: all participants who received at least one dose of the investigational product
    [26] - Safety Population: all participants who received at least one dose of the investigational product
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse event (AE) or serious adverse event (SAE) during Part 2

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    End point title
    Number of participants with any adverse event (AE) or serious adverse event (SAE) during Part 2
    End point description
    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (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 or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Part 2 up to Week 24 of Part 2 + 1 day
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [27]
    Units: Participants
    number (not applicable)
        Any AE
    69
        Any SAE
    9
    Notes
    [27] - Safety Population: all participants who received at least one dose of the investigational product
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated maximum toxicity grade for the indicated clinical chemistry parameters at any time post-Baseline (BL) during Part 1

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    End point title
    Number of participants with the indicated maximum toxicity grade for the indicated clinical chemistry parameters at any time post-Baseline (BL) during Part 1
    End point description
    Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE), version 4.0: Grade 0(G0), none; Grade 1(G1), mild; Grade 2(G2), moderate; Grade 3(G3), severe; Grade 4(G4), life-threatening or disabling. Parameters included: aspartate amino transferase(AST), alkaline phosphatase(ALP), total bilirubin, albumin, alanine amino transferase(ALT), prothrombin international normalized ratio(PT INR), activated partial thromboplastin time(APTT), and creatinine. The BL value is defined as the value taken at Day 1 or, if missing, the latest non-missing Screening value. For serum creatinine, due to the variations in creatinine, the average of the Screening and the Day 1 values will be used as BL. The maximum post-BL toxicity grade includes any scheduled or unscheduled post-BL assessment during Part 1. Only participants available at the specified time points were analyzed(represented by n=X,X in the category titles)
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 13 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [28]
    63 [29]
    Units: Participants
    number (not applicable)
        AST, G0, n=29, 63
    26
    50
        AST, G1, n=29, 63
    3
    12
        AST, G2, n=29, 63
    0
    1
        AST, G3, n=29, 63
    0
    0
        AST, G4, n=29, 63
    0
    0
        ALT, G0, n=29, 63
    27
    52
        ALT, G1, n=29, 63
    2
    6
        ALT, G2, n=29, 63
    0
    3
        ALT, G3, n=29, 63
    0
    2
        ALT, G4, n=29, 63
    0
    0
        Total Bilirubin, G0, n=29, 63
    29
    60
        Total Bilirubin, G1, n=29, 63
    0
    3
        Total Bilirubin, G2, n=29, 63
    0
    0
        Total Bilirubin, G3, n=29, 63
    0
    0
        Total Bilirubin, G4, n=29, 63
    0
    0
        Albumin, G0, n=29, 63
    29
    63
        Albumin, G1, n=29, 63
    0
    0
        Albumin, G2, n=29, 63
    0
    0
        Albumin, G3, n=29, 63
    0
    0
        Albumin, G4, n=29, 63
    0
    0
        ALP, G0, n=29, 63
    28
    47
        ALP, G1, n=29, 63
    1
    16
        ALP, G2, n=29, 63
    0
    0
        ALP, G3, n=29, 63
    0
    0
        ALP, G4, n=29, 63
    0
    0
        PT INR, G0, n=27, 58
    26
    57
        PT INR, G1, n=27, 58
    1
    1
        PT INR, G2, n=27, 58
    0
    0
        PT INR, G3, n=27, 58
    0
    0
        PT INR, G4, n=27, 58
    0
    0
        APTT, G0 n=27, 58
    13
    24
        APTT, G1, n=27, 58
    13
    32
        APTT, G2, n=27, 58
    1
    2
        APTT, G3, n=27, 58
    0
    0
        APTT, G4, n=27, 58
    0
    0
        Creatinine, G0, n=29, 63
    22
    47
        Creatinine, G1, n=29, 63
    7
    15
        Creatinine, G2, n=29, 63
    0
    1
        Creatinine, G3, n=29, 63
    0
    0
        Creatinine, G4, n=29, 63
    0
    0
    Notes
    [28] - Safety population
    [29] - Safety population
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated maximum toxicity grade for the indicated clinical chemistry parameters at any time post-Baseline during Part 2

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    End point title
    Number of participants with the indicated maximum toxicity grade for the indicated clinical chemistry parameters at any time post-Baseline during Part 2
    End point description
    Clinical chemistry parameters were summarized according to the NCI CTCAE, version 4.0: G0, none; G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Parameters included: AST, ALP, total bilirubin, albumin, ALT, and creatinine. For participants randomized to Placebo in Part 1, the BL value for Part 2 is defined as the value taken at Week 13 of Part 1. For serum creatinine, the value taken at Week 13 of Part 1 will be used as BL. For participants randomized to Eltrombopag in Part 1, the BL value is defined as the value taken on Day 1 or, if missing, the latest non-missing Screening value. For serum creatinine, due to the variations in creatinine, the average of the Screening and the Day 1 values will be used as BL. For participants who do not have both a Screening and Day 1 value, the Screening or Day 1 value will be used as BL. The maximum post-BL toxicity grade includes any scheduled or unscheduled post-BL assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline (BL) of Part 2 through Follow-up
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [30]
    Units: Participants
    number (not applicable)
        AST, G0
    63
        AST, G1
    21
        AST, G2
    1
        AST, G3
    2
        AST, G4
    0
        ALT, G0
    67
        ALT, G1
    14
        ALT, G2
    3
        ALT, G3
    3
        ALT, G4
    0
        Total Bilirubin, G0
    80
        Total Bilirubin, G1
    4
        Total Bilirubin, G2
    3
        Total Bilirubin, G3
    0
        Total Bilirubin, G4
    0
        Albumin, G0
    85
        Albumin, G1
    1
        Albumin, G2
    1
        Albumin, G3
    0
        Albumin, G4
    0
        ALP, G0
    67
        ALP, G1
    20
        ALP, G2
    0
        ALP, G3
    0
        ALP, G4
    0
        Creatinine, G0
    72
        Creatinine, G1
    14
        Creatinine, G2
    1
        Creatinine, G3
    0
        Creatinine, G4
    0
    Notes
    [30] - Safety Population. Only participants who entered Part 2 (Open-label eltrombopag phase) were analyzed
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated maximum toxicity grade for the indicated hematology parameters at any time post-Baseline during Part 1

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    End point title
    Number of participants with the indicated maximum toxicity grade for the indicated hematology parameters at any time post-Baseline during Part 1
    End point description
    Hematology parameters were summarized according to the NCI CTCAE, version 4.0: G0, none; G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Hematology parameters included: leukocytes, neutrophils, hemoglobin (increased), hemoglobin (anemia), lymphocytes (increased), and lymphocytes (decreased). The Baseline value is defined as the value taken at Day 1 or, if missing, the latest non-missing Screening value. The maximum post-Baseline toxicity grade includes any scheduled or unscheduled post-Baseline assessment during Part 1. Only those participants available at the specified time points were analyzed (represented by n=X,X in the category titles).
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 13 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [31]
    63 [32]
    Units: Participants
    number (not applicable)
        Leukocytes, G0, n=29, 63
    23
    50
        Leukocytes, G1, n=29, 63
    6
    11
        Leukocytes, G2, n=29, 63
    0
    0
        Leukocytes, G3, n=29, 63
    0
    1
        Leukocytes, G4, n=29, 63
    0
    1
        Neutrophils G0, n=29, 63
    27
    52
        Neutrophils G1, n=29, 63
    1
    3
        Neutrophils G2, n=29, 63
    0
    6
        Neutrophils G3, n=29, 63
    1
    0
        Neutrophils G4, n=29, 63
    0
    2
        Hemoglobin (increased), G0, n=29, 63
    26
    49
        Hemoglobin (increased), G1, n=29, 63
    3
    12
        Hemoglobin (increased), G2, n=29, 63
    0
    2
        Hemoglobin (increased), G3, n=29, 63
    0
    0
        Hemoglobin (increased), G4, n=29, 63
    0
    0
        Hemoglobin (anemia), G0, n=29, 63
    20
    42
        Hemoglobin (anemia), G1, n=29, 63
    7
    17
        Hemoglobin (anemia), G2, n=29, 63
    0
    4
        Hemoglobin (anemia), G3, n=29, 63
    2
    0
        Hemoglobin (anemia), G4, n=29, 63
    0
    0
        Lymphocytes (increased), G0, n=29, 63
    17
    37
        Lymphocytes (increased), G1, n=29, 63
    0
    0
        Lymphocytes (increased), G2, n=29, 63
    12
    26
        Lymphocytes (increased), G3, n=29, 63
    0
    0
        Lymphocytes (increased), G4, n=29, 63
    0
    0
        Lymphocytes (decreased), G0, n=29, 63
    25
    48
        Lymphocytes (decreased), G1, n=29, 63
    4
    13
        Lymphocytes (decreased), G2, n=29, 63
    0
    1
        Lymphocytes (decreased), G3, n=29, 63
    0
    1
        Lymphocytes (decreased), G4, n=29, 63
    0
    0
    Notes
    [31] - Safety population
    [32] - Safety population
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated maximum toxicity grade for the indicated hematology parameters at any time post-Baseline during Part 2

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    End point title
    Number of participants with the indicated maximum toxicity grade for the indicated hematology parameters at any time post-Baseline during Part 2
    End point description
    Hematology parameters were summarized according to the NCI CTCAE, version 4.0: G0, none, G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Hematology parameters included: leukocytes, neutrophils, hemoglobin (increased), hemoglobin (anemia), lymphocytes (increased), and lymphocytes (decreased). For participants randomized to Placebo in Part 1, the BL value for Part 2 is defined as the value taken at Week 13 of Part 1. For participants randomized to Eltrombopag in Part 1, the BL value is defined as the value taken on Day 1 or, if missing, the latest non-missing Screening value. For participants who do not have both a Screening and Day 1 value, the Screening or Day 1 value will be used as BL. The maximum post-BL toxicity grade includes any scheduled or unscheduled post-BL assessment.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 24 of Part 2 and Follow-up Weeks 1 to 4 (up to Study Week 41)
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [33]
    Units: Participants
    number (not applicable)
        Leukocytes, G0
    59
        Leukocytes, G1
    23
        Leukocytes, G2
    3
        Leukocytes, G3
    2
        Leukocytes, G4
    0
        Neutrophils, G0
    63
        Neutrophils, G1
    6
        Neutrophils, G2
    13
        Neutrophils, G3
    2
        Neutrophils, G4
    3
        Hemoglobin (increased), G0
    74
        Hemoglobin (increased), G1
    11
        Hemoglobin (increased), G2
    2
        Hemoglobin (increased), G3
    0
        Hemoglobin (increased), G4
    0
        Hemoglobin (anemia), G0
    48
        Hemoglobin (anemia), G1
    31
        Hemoglobin (anemia), G2
    7
        Hemoglobin (anemia), G3
    1
        Hemoglobin (anemia), G4
    0
        Lymphocytes (increased), G0
    47
        Lymphocytes (increased), G1
    0
        Lymphocytes (increased), G2
    40
        Lymphocytes (increased), G3
    0
        Lymphocytes (increased), G4
    0
        Lymphocytes (decreased), G0
    65
        Lymphocytes (decreased), G1
    19
        Lymphocytes (decreased), G2
    2
        Lymphocytes (decreased), G3
    1
        Lymphocytes (decreased), G4
    0
    Notes
    [33] - Safety Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed
    No statistical analyses for this end point

    Secondary: Number of participants (par) with vital sign data falling outside the reference ranges (RR) at the indicated visit during Part 1

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    End point title
    Number of participants (par) with vital sign data falling outside the reference ranges (RR) at the indicated visit during Part 1
    End point description
    Vital sign measurements were taken before blood draws and included systolic blood pressure(SBP), diastolic blood pressure(DBP), and heart rate(HR). The number of par are reported with vital sign data falling outside the standard RR: RR high(RRH) and RR low(RRL). The BL value is the value taken at Day 1 or if missing, the latest non-missing SCR value. RR for SBP or DBP (mmHg) are read: Lower Limit of Normal, Normal Range, Upper Limit of Normal. For Ages 1 to 5 years (yrs) ranges are SBP <85, 85 to 115, >115; DBP <45, 45 to70, >70. Ages 6 to 11 yrs: SBP <85, 85 to 120, >120;, DBP <50, 50 to 75, >75. Ages 12 to 17 yrs: SBP <95, 95 to 135, >135; DBP <55, 55 to 85, >85. RR for HR(bpm) are ages 1 to < 3 yrs: <90, 90 to 140, >140; ages 3 to < 5 yrs: <75, 75 to 130, >130, ages 5 to < 8yrs: <65, 65 to 115, >115; ages 8 to < 12yrs: <55, 55 to 110, >110; and ages 12 to 18 yrs: <55, 55 to 110, >110. Only par available at the specified time points were analyzed( n=X,X in the category title)
    End point type
    Secondary
    End point timeframe
    From Screening (SCR) up to Week 13 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [34]
    63 [35]
    Units: Participants
    number (not applicable)
        DBP, Day 1, RRH, n=28,62
    6
    8
        DBP, Day 1, RRL, n=28, 62
    2
    5
        DBP, Week 1, RRH, n=28, 63
    3
    10
        DBP, Week 1, RRL, n=28, 63
    0
    5
        DBP, Week 2, RRH, n=29, 63
    3
    8
        DBP, Week 2, RRL, n=29, 63
    2
    6
        DBP, Week 3, RRH, n=28, 63
    7
    12
        DBP, Week 3, RRL, n=28, 63
    2
    6
        DBP, Week 4, RRH, n=29, 62
    7
    5
        DBP, Week 4, RRL, n=29, 62
    2
    9
        DBP, Week 5, RRH, n=27, 62
    4
    10
        DBP, Week 5, RRL, n=27, 62
    2
    6
        DBP, Week 6, RRH, n=28, 62
    7
    10
        DBP, Week 6, RRL, n=28, 62
    1
    8
        DBP, Week 7, RRH, n=28, 63
    3
    7
        DBP, Week 7, RRL, n=28, 63
    2
    5
        DBP, Week 8, RRH, n=28, 63
    4
    9
        DBP, Week 8, RRL, n=28, 63
    2
    8
        DBP, Week 9, RRH, n=27, 61
    4
    9
        DBP, Week 9, RRL, n=27, 61
    2
    4
        DBP, Week 10, RRH, n=28, 62
    6
    8
        DBP, Week 10, RRL, n=28, 62
    2
    7
        DBP, Week 11, RRH, n=28, 61
    6
    8
        DBP, Week 11, RRL, n=28, 61
    3
    6
        DBP, Week 12, RRH, n=28, 61
    3
    8
        DBP, Week 12, RRL, n=28, 61
    0
    6
        DBP, Week 13, RRH, n=28, 61
    4
    9
        DBP, Week 13, RRL, n=28, 61
    3
    4
        Heart Rate, Day 1, RRH, n=28, 62
    0
    2
        Heart Rate, Day 1, RRL, n=28, 62
    0
    1
        Heart Rate, Week 1, RRH, n=28, 63
    0
    0
        Heart Rate, Week 1, RRL, n=28, 63
    0
    0
        Heart Rate, Week 2, RRH, n=29, 63
    2
    1
        Heart Rate, Week 2, RRL, n=29, 63
    0
    1
        Heart Rate, Week 3, RRH, n=28, 63
    1
    2
        Heart Rate, Week 3, RRL, n=28, 63
    0
    0
        Heart Rate, Week 4, RRH, n=29, 61
    0
    4
        Heart Rate, Week 4, RRL, n=29, 61
    0
    1
        Heart Rate, Week 5, RRH, n=27, 62
    1
    5
        Heart Rate, Week 5, RRL, n=27, 62
    1
    0
        Heart Rate, Week 6, RRH, n=28,62
    1
    1
        Heart Rate, Week 6, RRL, n=28, 62
    1
    0
        Heart Rate, Week 7, RRH, n=28, 63
    0
    2
        Heart Rate, Week 7, RRL, n=28, 63
    1
    0
        Heart Rate, Week 8, RRH, n=28, 63
    1
    2
        Heart Rate, Week 8, RRL, n=28, 63
    1
    0
        Heart Rate, Week 9, RRH, n=27, 61
    1
    2
        Heart Rate, Week 9, RRL, n=27, 61
    0
    0
        Heart Rate, Week 10, RRH, n=28, 62
    1
    1
        Heart Rate, Week 10, RRL, n=28, 62
    0
    0
        Heart Rate, Week 11, RRH, n=28, 61
    1
    2
        Heart Rate, Week 11, RRL, n=28, 61
    0
    0
        Heart Rate, Week 12, RRH, n=28,61
    0
    2
        Heart Rate, Week 12, RRL, n=28, 61
    0
    0
        Heart Rate, Week 13, RRH, n=28, 61
    0
    3
        Heart Rate, Week 13, RRL, n=28, 61
    1
    0
        SBP, Day 1, RRH, n=28, 62
    5
    10
        SBP, Day 1, RRL, n=28, 62
    3
    6
        SBP, Week 1, RRH, n=28, 63
    3
    11
        SBP, Week 1, RRL, n=28,63
    4
    8
        SBP, Week 2, RRH, n=29, 63
    4
    7
        SBP, Week 2, RRL, n=29, 63
    3
    9
        SBP, Week 3, RRH, n=28, 63
    3
    9
        SBP, Week 3, RRL, n=28, 63
    2
    9
        SBP, Week 4, RRH, n=29, 62
    3
    10
        SBP, Week 4, RRL, n=29, 62
    2
    9
        SBP, Week 5, RRH, n=27, 62
    5
    9
        SBP, Week 5, RRL, n=27, 62
    4
    7
        SBP, Week 6, RRH, n=28, 62
    5
    7
        SBP, Week 6, RRL, n=28, 62
    3
    8
        SBP, Week 7, RRH, n=28, 63
    5
    10
        SBP, Week 7, RRL, n=28, 63
    3
    7
        SBP, Week 8, RRH, n=28, 63
    3
    14
        SBP, Week 8, RRL, n=28, 63
    4
    7
        SBP, Week 9, RRH, n=27, 61
    4
    12
        SBP, Week 9, RRL, n=27, 61
    3
    7
        SBP, Week 10, RRH, n=28, 62
    4
    11
        SBP, Week 10, RRL, n=28, 62
    3
    11
        SBP, Week 11, RRH, n=28, 61
    6
    12
        SBP, Week 11, RRL, n=28, 61
    5
    9
        SBP, Week 12, RRH, n=28, 61
    4
    11
        SBP, Week 12, RRL, n=28, 61
    4
    4
        SBP, Week 13, RRH, n=28, 61
    6
    9
        SBP, Week 13, RRL, n=28, 61
    4
    7
    Notes
    [34] - Safety population
    [35] - Safety population
    No statistical analyses for this end point

    Secondary: Number of participants (par) with vital sign data falling outside the reference ranges (RR) at the indicated visit during Part 2

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    End point title
    Number of participants (par) with vital sign data falling outside the reference ranges (RR) at the indicated visit during Part 2
    End point description
    Vital sign measurements were taken before any blood draw and included systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate(HR). The number of par are reported with vital sign data falling outside the standard RR as RR high(RRH) and RR low(RRL) from SCR up to Week 24 of Part 2 and from Follow-up Week 1 to Week 4. RR for Blood Pressure(mmHg) are read as: Lower Limit of Normal, Normal Range, Upper Limit of Normal. For Ages 1 to 5 years (yrs) ranges are SBP <85, 85 to 115, >115; DBP <45, 45 to70, >70. Ages 6 to 11 yrs: SBP <85, 85 to 120, >120; DBP <50, 50 to 75, >75. Ages 12 to 17 yrs: SBP <95, 95 to 135, >135; DBP <55, 55 to 85, >85. RR for HR (bpm) are ages 1 to < 3 yrs: <90, 90 to 140, >140; ages 3 to < 5 yrs: <75, 75 to 130, >130, ages 5 to < 8yrs: <65, 65 to 115, >115; ages 8 to < 12yrs: <55, 55 to 110, >110; and ages 12 to 18 yrs: <55, 55 to 110, >110. Only par available at the specified time points were analyzed (represented by n=X in the category titles)
    End point type
    Secondary
    End point timeframe
    From Week 1 up to Week 24 of Part 2 and Follow-up Week 1 to Week 4 (up to Week 41)
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [36]
    Units: Participants
    number (not applicable)
        DBP, Week 1, RRH, n=87
    14
        DBP, Week 1, RRL, n=87
    8
        DBP, Week 2, RRH, n=86
    14
        DBP, Week 2, RRL, n=86
    8
        DBP, Week 3, RRH, n=86
    13
        DBP, Week 3, RRL, n=86
    11
        DBP, Week 4, RRH, n=68
    10
        DBP, Week 4, RRL, n=68
    7
        DBP, Week 5, RRH, n=61
    7
        DBP, Week 5, RRL, n=61
    7
        DBP, Week 6, RRH, n=55
    6
        DBP, Week 6, RRL, n=55
    4
        DBP, Week 7, RRH, n=52
    7
        DBP, Week 7, RRL, n=52
    5
        DBP, Week 8, RRH, n=53
    4
        DBP, Week 8, RRL, n=53
    6
        DBP, Week 9, RRH, n=45
    3
        DBP, Week 9, RRL, n=45
    7
        DBP, Week 10, RRH, n=42
    5
        DBP, Week 10, RRL, n=42
    7
        DBP, Week 11, RRH, n=40
    5
        DBP, Week 11, RRL, n=40
    7
        DBP, Week 12, RRH, n=63
    9
        DBP, Week 12, RRL, n=63
    11
        DBP, Week 13, RRH, n=29
    4
        DBP, Week 13, RRL, n=29
    2
        DBP, Week 14, RRH, n=38
    2
        DBP, Week 14, RRL, n=38
    9
        DBP, Week 15, RRH, n=43
    7
        DBP, Week 15, RRL, n=43
    3
        DBP, Week 16, RRH, n=47
    3
        DBP, Week 16, RRL, n=47
    6
        DBP, Week 17, RRH, n=37
    5
        DBP, Week 17, RRL, n=37
    6
        DBP, Week 18, RRH, n=34
    7
        DBP, Week 18, RRL, n=34
    5
        DBP, Week 19, RRH, n=44
    5
        DBP, Week 19, RRL, n=44
    3
        DBP, Week 20, RRH, n=39
    6
        DBP, Week 20, RRL, n=39
    3
        DBP, Week 21, RRH, n=41
    9
        DBP, Week 21, RRL, n=41
    6
        DBP, Week 22, RRH, n=34
    6
        DBP, Week 22, RRL, n=34
    3
        DBP, Week 23, RRH, n=36
    6
        DBP, Week 23, RRL, n=36
    6
        DBP, Week 24, RRH, n=79
    14
        DBP, Week 24, RRL, n=79
    10
        DBP, Follow-Up Week 1, RRH, n=29
    8
        DBP, Follow-Up Week 1, RRL, n=29
    3
        DBP, Follow-Up Week 2, RRH, n=37
    8
        DBP, Follow-Up Week 2, RRL, n=37
    6
        DBP, Follow-Up Week 3, RRH, n=39
    4
        DBP, Follow-Up Week 3, RRL, n=39
    5
        DBP, Follow-Up Week 4, RRH, n=67
    8
        DBP, Follow-Up Week 4, RRL, n=67
    5
        Heart Rate, Week 1, RRH, n=87
    4
        Heart Rate, Week 1, RRL, n=87
    1
        Heart Rate, Week 2, RRH, n=86
    3
        Heart Rate, Week 2, RRL, n=86
    2
        Heart Rate, Week 3, RRH, n=86
    1
        Heart Rate, Week 3, RRL, n=86
    0
        Heart Rate, Week 4, RRH, n=68
    2
        Heart Rate, Week 4, RRL, n=68
    0
        Heart Rate, Week 5, RRH, n=61
    0
        Heart Rate, Week 5, RRL, n=61
    1
        Heart Rate, Week 6, RRH, n=55
    1
        Heart Rate, Week 6, RRL, n=55
    0
        Heart Rate, Week 7, RRH, n=52
    2
        Heart Rate, Week 7, RRL, n=52
    0
        Heart Rate, Week 8, RRH, n=53
    2
        Heart Rate, Week 8, RRL, n=53
    0
        Heart Rate, Week 9, RRH, n=45
    2
        Heart Rate, Week 9, RRL, n=45
    0
        Heart Rate, Week 10, RRH, n=42
    1
        Heart Rate, Week 10, RRL, n=42
    1
        Heart Rate, Week 11, RRH, n=40
    1
        Heart Rate, Week 11, RRL, n=40
    1
        Heart Rate, Week 12, RRH, n=63
    1
        Heart Rate, Week 12, RRL, n=63
    1
        Heart Rate, Week 13, RRH, n=29
    2
        Heart Rate, Week 13, RRL, n=29
    0
        Heart Rate, Week 14, RRH, n=38
    2
        Heart Rate, Week 14, RRL, n=38
    1
        Heart Rate, Week 15, RRH, n=43
    0
        Heart Rate, Week 15, RRL, n=43
    0
        Heart Rate, Week 16, RRH, n=47
    2
        Heart Rate, Week 16, RRL, n=47
    0
        Heart Rate, Week 17, RRH, n=37
    2
        Heart Rate, Week 17, RRL, n=37
    1
        Heart Rate, Week 18, RRH, n=34
    0
        Heart Rate, Week 18, RRL, n=34
    0
        Heart Rate, Week 19, RRH, n=44
    0
        Heart Rate, Week 19, RRL, n=44
    1
        Heart Rate, Week 20, RRH, n=39
    2
        Heart Rate, Week 20, RRL, n=39
    0
        Heart Rate, Week 21, RRH, n=41
    0
        Heart Rate, Week 21, RRL, n=41
    0
        Heart Rate, Week 22, RRH, n=34
    2
        Heart Rate, Week 22, RRL, n=34
    0
        Heart Rate, Week 23, RRH, n=36
    0
        Heart Rate, Week 23, RRL, n=36
    0
        Heart Rate, Week 24, RRH, n=79
    1
        Heart Rate, Week 24, RRL, n=79
    1
        Heart Rate, Follow-Up Week 1, RRH, n=29
    1
        Heart Rate, Follow-Up Week 1, RRL, n=29
    0
        Heart Rate, Follow-Up Week 2, RRH, n=37
    2
        Heart Rate, Follow-Up Week 2, RRL, n=37
    1
        Heart Rate, Follow-Up Week 3, RRH, n=39
    2
        Heart Rate, Follow-Up Week 3, RRL, n=39
    0
        Heart Rate, Follow-Up Week 4, RRH, n=67
    2
        Heart Rate, Follow-Up Week 4, RRL, n=67
    2
        SBP, Week 1, RRH, n=87
    13
        SBP, Week 1, RRL, n=87
    9
        SBP, Week 2, RRH, n=86
    19
        SBP, Week 2, RRL, n=86
    16
        SBP, Week 3, RRH, n=86
    15
        SBP, Week 3, RRL, n=86
    13
        SBP, Week 4, RRH, n=68
    10
        SBP, Week 4, RRL, n=68
    7
        SBP, Week 5, RRH, n=61
    7
        SBP, Week 5, RRL, n=61
    8
        SBP, Week 6, RRH, n=55
    11
        SBP, Week 6, RRL, n=55
    7
        SBP, Week 7, RRH, n=52
    10
        SBP, Week 7, RRL, n=52
    5
        SBP, Week 8, RRH, n=53
    8
        SBP, Week 8, RRL, n=53
    5
        SBP, Week 9, RRH, n=45
    8
        SBP, Week 9, RRL, n=45
    9
        SBP, Week 10, RRH, n=42
    4
        SBP, Week 10, RRL, n=42
    4
        SBP, Week 11, RRH, n=40
    4
        SBP, Week 11, RRL, n=40
    6
        SBP, Week 12, RRH, n=63
    14
        SBP, Week 12, RRL, n=63
    10
        SBP, Week 13, RRH, n=29
    3
        SBP, Week 13, RRL, n=29
    2
        SBP, Week 14, RRH, n=38
    5
        SBP, Week 14, RRL, n=38
    7
        SBP, Week 15, RRH, n=43
    9
        SBP, Week 15, RRL, n=43
    7
        SBP, Week 16, RRH, n=47
    7
        SBP, Week 16, RRL, n=47
    6
        SBP, Week 17, RRH, n=37
    9
        SBP, Week 17, RRL, n=37
    4
        SBP, Week 18, RRH, n=34
    6
        SBP, Week 18, RRL, n=34
    5
        SBP, Week 19, RRH, n=44
    7
        SBP, Week 19, RRL, n=44
    4
        SBP, Week 20, RRH, n=39
    5
        SBP, Week 20, RRL, n=39
    5
        SBP, Week 21, RRH, n=41
    10
        SBP, Week 21, RRL, n=41
    6
        SBP, Week 22, RRH, n=34
    6
        SBP, Week 22, RRL, n=34
    4
        SBP, Week 23, RRH, n=36
    6
        SBP, Week 23, RRL, n=36
    3
        SBP, Week 24, RRH, n=79
    13
        SBP, Week 24, RRL, n=79
    12
        SBP, Follow-Up Week 1, RRH, n=29
    5
        SBP, Follow-Up Week 1, RRL, n=29
    3
        SBP, Follow-Up Week 2, RRH, n=37
    5
        SBP, Follow-Up Week 2, RRL, n=37
    7
        SBP, Follow-Up Week 3, RRH, n=39
    9
        SBP, Follow-Up Week 3, RRL, n=39
    4
        SBP, Follow-Up Week 4, RRH, n=67
    9
        SBP, Follow-Up Week 4, RRL, n=67
    7
    Notes
    [36] - Safety population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with a change in visual acuity since Baseline at Week 12 of Part 1

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    End point title
    Number of participants with a change in visual acuity since Baseline at Week 12 of Part 1
    End point description
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Change in visual acuity results are presented as No (no change from Baseline), Not Clinically Significant (NCS), Improvement, and Worsening since Baseline. The Baseline value was obtained at the Screening Visit.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    29 [37]
    63 [38]
    Units: Participants
    number (not applicable)
        No Change
    22
    47
        NCS
    4
    8
        Improvement
    1
    2
        Worsening
    0
    1
        Not Measured
    2
    5
    Notes
    [37] - Safety population
    [38] - Safety population
    No statistical analyses for this end point

    Secondary: Number of participants with a change in visual acuity since Baseline at Week 24 of Part 2

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    End point title
    Number of participants with a change in visual acuity since Baseline at Week 24 of Part 2
    End point description
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Change in visual acuity results are presented as No Change, NCS, Improvement, and Worsening since Baseline. The Baseline value was obtained at the Screening Visit.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [39]
    Units: Participants
    number (not applicable)
        No Change
    58
        NCS
    13
        Improvement
    3
        Worsening
    6
        Not Measured
    7
    Notes
    [39] - Safety population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with a change in visual acuity since Baseline at Follow-Up Week 24

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    End point title
    Number of participants with a change in visual acuity since Baseline at Follow-Up Week 24
    End point description
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Change in visual acuity results are presented as No Change, NCS, Improvement, and Worsening since Baseline. The Baseline value was obtained at the Screening Visit.
    End point type
    Secondary
    End point timeframe
    Baseline and Follow-Up Week 24 (Study Week 61)
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    87 [40]
    Units: Participants
    number (not applicable)
        No Change
    63
        NCS
    12
        Improvement
    9
        Worsening
    2
        Not Measured
    1
    Notes
    [40] - Safety population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with worsening visual acuity due to cataracts at Week 12 of Part 1

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    End point title
    Number of participants with worsening visual acuity due to cataracts at Week 12 of Part 1
    End point description
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with worsening visual acuity due to cataracts at Week 12 of Part 1 are presented. Change due to cataracts is categorized as "Yes" or "No". Only those participants who had a result of ‘worsening’ in assessment of change of visual acuity at this timepoint were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 of Part 1
    End point values
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag
    Number of subjects analysed
    0 [41]
    1 [42]
    Units: Participants
    number (not applicable)
        Yes
    0
        No
    1
    Notes
    [41] - Safety population
    [42] - Safety population
    No statistical analyses for this end point

    Secondary: Number of participants with worsening visual acuity due to cataracts at Week 24 of Part 2

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    End point title
    Number of participants with worsening visual acuity due to cataracts at Week 24 of Part 2
    End point description
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with worsening visual acuity due to cataracts at Week 24 of Part 2 are presented. Change due to cataracts is categorized as "Yes" or "No".
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24 of Part 2
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    6 [43]
    Units: Participants
    number (not applicable)
        Yes
    1
        No
    5
    Notes
    [43] - Safety Population. Only participants who had worsening visual acuity at Week 24 were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with worsening visual acuity due to cataracts at Follow-Up Week 24

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    End point title
    Number of participants with worsening visual acuity due to cataracts at Follow-Up Week 24
    End point description
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with worsening visual acuity due to cataracts at Follow-up Week 24 are presented. Change due to cataracts is categorized as "Yes" or "No".
    End point type
    Secondary
    End point timeframe
    Baseline and Follow-Up Week 24 (Week 61)
    End point values
    Part 2 (Open-Label Period) - Eltrombopag
    Number of subjects analysed
    2 [44]
    Units: Participants
    number (not applicable)
        Yes
    0
        No
    2
    Notes
    [44] - Safety population. Only those participants who had worsening visual acuity at Week 61 were analyzed.
    No statistical analyses for this end point

    Secondary: Pharmacokinetic (PK) assessments for eltrombopag for AUC (0-t)

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    End point title
    Pharmacokinetic (PK) assessments for eltrombopag for AUC (0-t)
    End point description
    Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. AUC(0-t) is defined as the area under the concentration-time curve over the dosing interval. The AUC(0-t) for a 50mg dose was estimated for each cohort. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.
    End point type
    Secondary
    End point timeframe
    Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
    End point values
    Eltrombopag Cohort 1 (12-17 years) Eltrombopag Cohort 2 (6-11 years) Eltrombopag Cohort 3 (1-5 years)
    Number of subjects analysed
    33 [45]
    38 [46]
    19 [47]
    Units: micrograms*hour per milliliter (ug.h/mL)
        geometric mean (confidence interval 95%)
    104 (86.1 to 126)
    171 (147 to 200)
    184 (147 to 230)
    Notes
    [45] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [46] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [47] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    No statistical analyses for this end point

    Secondary: Pharmacokinetic (PK) assessments for eltrombopag for apparent oral clearance (CL/F) and apparent intercompartmental clearance (Q/F)

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    End point title
    Pharmacokinetic (PK) assessments for eltrombopag for apparent oral clearance (CL/F) and apparent intercompartmental clearance (Q/F)
    End point description
    Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. CL/F is defined as the apparent oral clearance from plasma and Q/F is defined as apparent intercompartmental clearance. These parameters are dose independent. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort.
    End point type
    Secondary
    End point timeframe
    Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
    End point values
    Eltrombopag Cohort 1 (12-17 years) Eltrombopag Cohort 2 (6-11 years) Eltrombopag Cohort 3 (1-5 years)
    Number of subjects analysed
    33 [48]
    38 [49]
    19 [50]
    Units: Liters per hour (L/hr)
    geometric mean (confidence interval 95%)
        CL/F
    0.48 (0.4 to 0.58)
    0.29 (0.25 to 0.34)
    0.19 (0.15 to 0.24)
        Q/F
    0.61 (0.54 to 0.68)
    0.38 (0.34 to 0.42)
    0.24 (0.2 to 0.28)
    Notes
    [48] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [49] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [50] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    No statistical analyses for this end point

    Secondary: PK assessments for eltrombopag for apparent central volume (Vc/F) and apparent peripheral volume (Vp/F)

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    End point title
    PK assessments for eltrombopag for apparent central volume (Vc/F) and apparent peripheral volume (Vp/F)
    End point description
    Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. Vc/F is defined as the volume of the central (e.g. plasma) compartment and Vp/F is defined as the volume of the peripheral compartment. These parameters are dose independent. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort.
    End point type
    Secondary
    End point timeframe
    PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    End point values
    Eltrombopag Cohort 1 (12-17 years) Eltrombopag Cohort 2 (6-11 years) Eltrombopag Cohort 3 (1-5 years)
    Number of subjects analysed
    33 [51]
    38 [52]
    19 [53]
    Units: Liters (L)
    geometric mean (confidence interval 95%)
        Vc/F
    2.46 (2.2 to 2.75)
    1.57 (1.35 to 1.81)
    0.9 (0.76 to 1.05)
        Vp/F
    19.2 (17.7 to 20.9)
    11.8 (10.9 to 12.9)
    7.17 (6.58 to 7.81)
    Notes
    [51] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [52] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [53] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    No statistical analyses for this end point

    Secondary: Population PK model point estimate for eltrombopag for absorption rate-constant (Ka)

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    End point title
    Population PK model point estimate for eltrombopag for absorption rate-constant (Ka)
    End point description
    Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. Ka is defined as the absorption rate constant. This parameter is dose independent, and the population estimate Ka is reported.
    End point type
    Secondary
    End point timeframe
    Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
    End point values
    Eltrombopag Cohort 1 (12-17 years) Eltrombopag Cohort 2 (6-11 years) Eltrombopag Cohort 3 (1-5 years)
    Number of subjects analysed
    33 [54]
    38 [55]
    19 [56]
    Units: Units:1/h
        number (not applicable)
    0.189
    0.189
    0.189
    Notes
    [54] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [55] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [56] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    No statistical analyses for this end point

    Secondary: Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax

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    End point title
    Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax
    End point description
    Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. Cmax is defined as the maximum observed concentration. The Cmax for a 50mg dose was estimated for each cohort. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.
    End point type
    Secondary
    End point timeframe
    Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)
    End point values
    Eltrombopag Cohort 1 (12-17 years) Eltrombopag Cohort 2 (6-11 years) Eltrombopag Cohort 3 (1-5 years)
    Number of subjects analysed
    33 [57]
    38 [58]
    19 [59]
    Units: micrograms per milliliter (ug/mL)
        geometric mean (confidence interval 95%)
    6.94 (5.96 to 8.08)
    11.2 (9.91 to 12.8)
    12.5 (10.7 to 14.6)
    Notes
    [57] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [58] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    [59] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment adverse events (AEs) and serious adverse events (SAEs) are defined as events occuring from the start of investigational product until follow up (up to 61 weeks).
    Adverse event reporting additional description
    SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had received at least one dose of the investigational product.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Part 1 (Randomized Period)-Placebo
    Reporting group description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kilograms (kg) received placebo 37.5 milligrams (mg) once daily (QD), and those with a body weight >=27 kg received placebo 50 mg QD. Participants of East Asian ancestry received a starting dose of placebo 25 mg QD. Participants aged between 1 and 5 years received placebo 1.2 milligrams per kilogram (mg/kg) QD; participants of East Asian ancestry received a starting dose of placebo 0.8 milligrams per kilograms per day (mg/kg/day).

    Reporting group title
    Part 1 (Randomized Period)-Eltrombopag
    Reporting group description
    In Part 1, participants aged between 6 and 17 years with a body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD. Participants aged between 1 and 5 years received eltrombopag 1.2 mg/kg QD; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day.

    Reporting group title
    Part 2: Eltrombopag
    Reporting group description
    In Part 2, participants continued on the same dose of eltrombopag recevied in Part 1 unless adjustments were warranted according to the dosing guidelines.

    Serious adverse events
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag Part 2: Eltrombopag
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 29 (13.79%)
    5 / 63 (7.94%)
    9 / 87 (10.34%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 63 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 63 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase abnormal
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase abnormal
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemolytic anaemia
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 63 (0.00%)
    2 / 87 (2.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhinitis allergic
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Petechiae
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 63 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gingivitis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 63 (1.59%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhinitis
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         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
    Part 1 (Randomized Period)-Placebo Part 1 (Randomized Period)-Eltrombopag Part 2: Eltrombopag
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 29 (37.93%)
    37 / 63 (58.73%)
    56 / 87 (64.37%)
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 29 (0.00%)
    4 / 63 (6.35%)
    7 / 87 (8.05%)
         occurrences all number
    0
    4
    7
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    6 / 87 (6.90%)
         occurrences all number
    0
    0
    6
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    5 / 29 (17.24%)
    8 / 63 (12.70%)
    11 / 87 (12.64%)
         occurrences all number
    7
    23
    26
    Cough
         subjects affected / exposed
    0 / 29 (0.00%)
    7 / 63 (11.11%)
    8 / 87 (9.20%)
         occurrences all number
    0
    8
    9
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 29 (10.34%)
    6 / 63 (9.52%)
    8 / 87 (9.20%)
         occurrences all number
    3
    9
    15
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 29 (3.45%)
    4 / 63 (6.35%)
    9 / 87 (10.34%)
         occurrences all number
    1
    4
    12
    Influenza like illness
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    5 / 87 (5.75%)
         occurrences all number
    0
    0
    5
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 29 (0.00%)
    6 / 63 (9.52%)
    7 / 87 (8.05%)
         occurrences all number
    0
    10
    12
    Vomiting
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 63 (3.17%)
    6 / 87 (6.90%)
         occurrences all number
    3
    2
    11
    Diarrhoea
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    5 / 87 (5.75%)
         occurrences all number
    0
    0
    6
    Abdominal pain upper
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 63 (4.76%)
    0 / 87 (0.00%)
         occurrences all number
    4
    3
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 29 (6.90%)
    11 / 63 (17.46%)
    7 / 87 (8.05%)
         occurrences all number
    2
    11
    8
    Rhinitis
         subjects affected / exposed
    2 / 29 (6.90%)
    10 / 63 (15.87%)
    0 / 87 (0.00%)
         occurrences all number
    2
    11
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 29 (3.45%)
    7 / 63 (11.11%)
    9 / 87 (10.34%)
         occurrences all number
    1
    8
    10
    Pharyngitis
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    7 / 87 (8.05%)
         occurrences all number
    0
    0
    7
    Respiratory tract infection
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 63 (0.00%)
    6 / 87 (6.90%)
         occurrences all number
    0
    0
    9

    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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