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    Clinical Trial Results:
    Study PMA112509, a Phase I/II Study of Eltrombopag in Thrombocytopenic Subjects with Advanced Myelodysplastic Syndrome (MDS) or secondary Acute Myeloid Leukemia after MDS (sAML/MDS)

    Summary
    EudraCT number
    		 2009-015512-17
    Trial protocol
    		 DE   FR   DK   GB  
    Global end of trial date
    05 Dec 2013

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

    Trial information

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    Trial identification
    Sponsor protocol code
    PMA112509
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    09 Jul 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Dec 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of eltrombopag when administered to subjects with advanced MDS, sAML/MDS or de novo AML with 10-50% bone marrow blasts.
    Protection of trial subjects
    Participants were monitored closely throughout the study related to changes to bone marrow changes and disease progression. Bone marrow samples were taken prior to first dose of study medication and throughout the study until the end of the study. Bone marrow samples were reviewed centrally by a central pathologist. To closely monitor disease progression, the study implemented a blinded adjudication of disease progression by use of an adjudication committee comprised of three external hematologists.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 May 2009
    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
    Hong Kong: 10
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Brazil: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    United States: 25
    Country: Number of subjects enrolled
    Taiwan: 9
    Worldwide total number of subjects
    98
    EEA total number of subjects
    43
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    19
    From 65 to 84 years
    72
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The initial on-therapy phase of the study involved treatment with study medication for up to 6 months. After completion of the dosing period, participants (par.) underwent follow-up assessments for 6 months after the final dose. The 6-month Follow up period was intended to assess the long-term safety of treatment with eltrombopag.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Matching placebo tablets were administered to participants once daily for 6 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    placebo tablets orally once daily for 6 months

    Arm title
    		 Eltrombopag 50 mg
    Arm description
    		 Participants initially received 50 milligram (mg) eltrombopag tablets orally once daily for 6 months. Intra-individual dose adjustments in a stepwise fashion to 100 mg, 200 mg, or 300 mg were allowed based on the participants' platelet and bone marrow blast counts. For participants of East Asian heritage, a maximum dose of 150 mg was allowed. Stepwise dose adjustments from 50 mg to 100 mg or 150 mg were permitted for East Asian participants.
    Arm type
    		 Experimental

    Investigational medicinal product name
    eltrombopag
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 milligram (mg) eltrombopag tablets orally once daily for 6 months. Intra-individual dose adjustments in a stepwise fashion to 100 mg, 200 mg, or 300 mg were allowed based on the participants' platelet and bone marrow blast counts. For participants of East Asian heritage, a maximum dose of 150 mg was allowed. Stepwise dose adjustments from 50 mg to 100 mg or 150 mg were permitted for East Asian participants.

    Number of subjects in period 1
    		Placebo Eltrombopag 50 mg
    Started
    34
    64
    Completed
    3
    11
    Not completed
    31
    53
         Consent withdrawn by subject
    6
    9
         Physician decision
    -
    2
         Adverse event, non-fatal
    10
    10
         Disease Progression
    10
    21
         Lack of efficacy
    5
    9
         Protocol deviation
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo tablets were administered to participants once daily for 6 months.

    Reporting group title
    Eltrombopag 50 mg
    Reporting group description
    		 Participants initially received 50 milligram (mg) eltrombopag tablets orally once daily for 6 months. Intra-individual dose adjustments in a stepwise fashion to 100 mg, 200 mg, or 300 mg were allowed based on the participants' platelet and bone marrow blast counts. For participants of East Asian heritage, a maximum dose of 150 mg was allowed. Stepwise dose adjustments from 50 mg to 100 mg or 150 mg were permitted for East Asian participants.

    Reporting group values
    		 Placebo Eltrombopag 50 mg Total
    Number of subjects
    		 34 64 98
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    		 71 (40 to 91) 73 (29 to 88) -
    Gender categorical
    Units: Subjects
        Female
    		 9 30 39
        Male
    		 25 34 59
    Race
    Units: Subjects
        African American/African Heritage
    		 2 2 4
        Japanese/East Asian Heritage (EAH)/South EAH
    		 7 18 25
        White
    		 25 43 68
        African American/African Heritage & White
    		 0 1 1
    Number of participants with MDS or AML at Baseline per World Health Organization (WHO) Guidelines
    Two participants (1 placebo, 1 eltrombopag) had missing information.
    Units: Subjects
        Advanced Myelodysplastic Syndrome (AMS)
    		 11 15 26
        Acute Myeloid Leukemia (AML)
    		 22 48 70
        Missing
    		 1 1 2
    Number of participants with MDS or AML per French-American-Bristish Criteria
    Two participants (1 placebo, 1 eltrombopag) had missing information.
    Units: Subjects
        Advanced Myelodysplastic Syndrome
    		 14 22 36
        Acute Myeloid Leukemia
    		 19 41 60
        Missing
    		 1 1 2
    Median Bone Marrow Blast Counts at Baseline
    Bone marrow blasts are immature cells in the bone marrow.
    Units: percent
        median (full range (min-max))
    		 20 (10 to 50) 25.5 (10 to 50) -
    Median Absolute Neutrophil Count at Baseline
    Units: Giga (10^9) per Liter (Gi/L)
        median (full range (min-max))
    		 0.55 (0 to 9.8) 0.85 (0 to 17.6) -
    Median Platelet Count at Baseline
    Units: Gi/L
        median (full range (min-max))
    		 12.3 (2 to 38) 17.4 (2 to 71) -
    Median Hemoglobin Values at Baseline
    Units: grams per Liter
        median (full range (min-max))
    		 85 (60 to 112) 88 (43 to 132) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo tablets were administered to participants once daily for 6 months.

    Reporting group title
    Eltrombopag 50 mg
    Reporting group description
    		 Participants initially received 50 milligram (mg) eltrombopag tablets orally once daily for 6 months. Intra-individual dose adjustments in a stepwise fashion to 100 mg, 200 mg, or 300 mg were allowed based on the participants' platelet and bone marrow blast counts. For participants of East Asian heritage, a maximum dose of 150 mg was allowed. Stepwise dose adjustments from 50 mg to 100 mg or 150 mg were permitted for East Asian participants.

    Primary: Number of participants with any Serious Adverse Event (SAE) and non-serious Adverse Event (AE)

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    End point title
    		 Number of participants with any Serious Adverse Event (SAE) and non-serious Adverse Event (AE) [1]
    End point description
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is a Grade 4 (life threatening or disabling) non-hematologic laboratory abnormality assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Refer to the general AE/SAE module for a complete list of AEs and SAEs.
    End point type
    Primary
    End point timeframe
    From the start of study treatment plus 30 days post-treatment (average of 96.6 weeks)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical Analysis is not applicable for this Outcome Measure.
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [2]
    64 [3]
    Units: Participants
        Any Adverse Event
    32
    63
        Any Serious Adverse Event
    22
    50
    Notes
    [2] - Safety Population: all randomized par. who received at least one dose of investigation product.
    [3] - Safety Population: all randomized par. who received at least one dose of investigation product.
    No statistical analyses for this end point

    Primary: Bone marrow blast counts at Baseline, at Month 3, at Month 6, and at the 3-Month Follow-up visit, as Assessed by the Central Morphologist

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    End point title
    		 Bone marrow blast counts at Baseline, at Month 3, at Month 6, and at the 3-Month Follow-up visit, as Assessed by the Central Morphologist [4]
    End point description
    Bone marrow blast (immature cells in the bone marrow) counts were assessed every 3 months during the treatment and follow-up periods. Bone marrow exams occurring within 120 days of Baseline were slotted as Month 3, while those occurring after 120 days from Baseline were slotted as Month 6. Similar slotting was used for follow-up and extension periods. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points; thus, the overall number of participants analyzed reflects everyone in the Safety Population.
    End point type
    Primary
    End point timeframe
    Baseline, Month 3, Month 6, and at the 3-Month Follow-up visit (up to Study Month 18)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical Analysis is not applicable for this Outcome Measure.
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [5]
    64 [6]
    Units: percent
    median (inter-quartile range (Q1-Q3))
        Baseline, n=24, 56
    29 (13.5 to 38)
    31 (17 to 53.5)
        Month 3, n=14, 33
    42.5 (25 to 66)
    48 (21 to 73)
        Month 6, n=3, 10
    50 (8 to 74)
    38.5 (18 to 82)
        3-Month Follow-up visit, n=1, 6
    28 (28 to 28)
    49 (38 to 71)
    Notes
    [5] - Safety Population
    [6] - Safety Population
    No statistical analyses for this end point

    Primary: Number of participants with the indicated non-hematological laboratory toxicity >=Grade 3 post-Baseline

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    End point title
    		 Number of participants with the indicated non-hematological laboratory toxicity >=Grade 3 post-Baseline [7]
    End point description
    A grading (severity) scale is provided for each non-hematological laboratory toxicity. Grade refers to the severity of the toxicity. The CTCAE version 3.0 displays Grades 1 through 5, with unique clinical descriptions of the severity for each toxicity based on the general guideline: Grade 1, mild toxicity; Grade 2, moderate toxicity; Grade 3, severe toxicity; Grade 4, life-threatening or disabling toxicity; Grade 5, death related to toxicity.
    End point type
    Primary
    End point timeframe
    From the start of study treatment plus 30 days post-treatment (average of 96.6 weeks)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical Analysis is not applicable for this Outcome Measure.
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [8]
    64 [9]
    Units: Participants
        Alanine Amino Tranferase
    1
    1
        Albumin
    1
    0
        Alkaline Phosphatase
    1
    0
        Creatinine
    0
    1
        Hyperkalemia
    0
    1
        Hypokalemia
    2
    9
        Hyponatremia
    3
    3
        Total Bilirubin
    2
    2
    Notes
    [8] - Safety Population
    [9] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants classified as platelet responders

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    End point title
    		 Number of participants classified as platelet responders
    End point description
    Platelet responders were defined based on the modified International Working Group response criteria for hematological improvement as par. who had a Baseline platelet count <20 giga (10^9) cells per liter (Gi/L) and an increase to >20 Gi/L and at least a two times increase from Baseline, or a Baseline platelet count >=20 Gi/L and an increase to >=50 Gi/L and at least a two times increase from Baseline at any time during treatment with study medication (unless the increase in platelets is observed up to 3 days after a platelet transfusion). A durable platelet response is defined as a continuous platelet response of 4 weeks or longer. Analysis was performed by Stratified Cochrane-Mantel-haenszel chi-square test adjusting for the presence of a poor prognosis karyotype and bone marrow blast counts. Par. were evaluated according to the treatment to which they were randomized. Any participant who received a treatment randomization number was considered to have been randomized.
    End point type
    Secondary
    End point timeframe
    Baseline through the end of treatment (up to Study Week 81)
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [10]
    64 [11]
    Units: Participants
        Platelet response, yes
    10
    18
        Durable response, yes
    1
    5
    Notes
    [10] - All Randomized Population: all randomized participants.
    [11] - All Randomized Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Eltrombopag 50 mg
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 = 0.9419
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.9658
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3811
         upper limit
    		 2.4476
    Notes
    [12] - Statistical analysis for platelet response.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v Eltrombopag 50 mg
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.3586
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.7817
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2989
         upper limit
    		 25.8867
    Notes
    [13] - Statistical analysis for durable platelet response.

    Secondary: Number of participants with a platelet transfusion at the indicated study week

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    End point title
    		 Number of participants with a platelet transfusion at the indicated study week
    End point description
    The number of participants receiving platelet transfusions during the treatment period was assessed.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 4, 8, 12, 16, 20, and 24
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    32 [14]
    58 [15]
    Units: Participants
        Week 1, n=32, 58
    17
    29
        Week 4, n=26, 48
    12
    20
        Week 8, n=19, 39
    6
    12
        Week 12, n=9, 22
    4
    6
        Week 16, n=5, 13
    2
    4
        Week 20, n=4, 11
    2
    5
        Week 24, n=2, 5
    0
    3
    Notes
    [14] - All Randomized Population. Par. with data available at the indicated time points were analyzed.
    [15] - All Randomized Population. Par. with data available at the indicated time points were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with maximum platelet transfusion independence of >=56 days

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    End point title
    		 Number of participants with maximum platelet transfusion independence of >=56 days
    End point description
    For participants who received study medication, the duration of platelet transfusion independence is defined as the duration of time during which participants don’t receive any platelet transfusions during the treatment and 4-week follow up periods. Data are presented as the number of participants with platelet transfusion indpendence >=56 days. Analysis was performed by stratified Cochrane-Mantel-haenszel chi-square test adjusting for the presence of a poor prognosis karyotype and bone marrow blast counts.
    End point type
    Secondary
    End point timeframe
    During treatment plus 4 weeks of follow-up (up to Study Week 68.6)
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [16]
    64 [17]
    Units: participants
    7
    24
    Notes
    [16] - All Randomized Population
    [17] - All Randomized Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Eltrombopag 50 mg
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0979
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.277
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8558
         upper limit
    		 6.0585

    Secondary: Number of participants with bleeding events of the indicated severity

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    End point title
    		 Number of participants with bleeding events of the indicated severity
    End point description
    The severity of bleeding events was assessed using the World Health Organization bleeding scale: Grade 0, no bleeding; Grade 1, petechiae (pinpoint-sized bleeding); Grade 2, mild blood loss; Grade 3, gross blood loss; Grade 4, debilitating blood loss.
    End point type
    Secondary
    End point timeframe
    Day 1 and Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [18]
    64 [19]
    Units: Participants
        Day 1, Grade 0, n=34, 64
    15
    32
        Day 1, Grades, 1–4 n=34, 64
    19
    32
        Week 4, Grade 0, n=26, 45
    9
    23
        Week 4, Grades 1-4, n=26, 45
    17
    22
        Week 8, Grade 0, n=19, 28
    6
    21
        Week 8, Grades 1-4, n=19, 28
    13
    17
        Week 12, Grade 0, n=9, 21
    3
    13
        Week 12, Grades 1-4, n=9, 21
    6
    8
        Week 16, Grade 0, n=5, 13
    3
    5
        Week 16, Grades 1-4, n=5, 13
    2
    8
        Week 20, Grade 0, n=4, 11
    2
    5
        Week 20, Grades 1-4, n=4, 11
    2
    6
        Week 24, Grade 0, n=2, 5
    1
    3
        Week 24, Grades 1-4, n=2, 5
    1
    2
    Notes
    [18] - All Randomized Population. Par. with data available at the indicated time points were analyzed.
    [19] - All Randomized Population. Par. with data available at the indicated time points were analyzed.
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival is defined as the time from randomization until death due to any cause. For surviving participants and participants who withdrew from the study, time to death was censored at the time of last contact. Overall survival was summarized using Kaplan-Meier survival curves, and compared between treatment arms using a stratified log-rank. Hazard ratio was estimated using the Pike Estimator. A hazard ratio <1 indicates a lower risk with eltrombopag compared with placebo.
    End point type
    Secondary
    End point timeframe
    From randomization until death due to any cause (up to Study Week 96.6)
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [20]
    64 [21]
    Units: Weeks
        median (confidence interval 95%)
    15.7 (9.6 to 26.3)
    27 (16.4 to 34)
    Notes
    [20] - All Randomized Population
    [21] - All Randomized Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Eltrombopag 50 mg
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2079
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 1.27

    Secondary: Mean steady-state plasma eltrombopag trough concentrations by dose level

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    End point title
    		 Mean steady-state plasma eltrombopag trough concentrations by dose level [22]
    End point description
    Mean steady-state plasma eltrombopag concentrations were estimated for different dose levels. Only those participants with data available at the indicated time points were analyzed. A single participant could have received more than one dose of eltrombopag.
    End point type
    Secondary
    End point timeframe
    Steady-state (>=5 days on current dose) and within 6 hours of the planned sample time
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical Analysis is not applicable for this Outcome Measure.
    End point values
    		 Eltrombopag 50 mg
    Number of subjects analysed
    64 [23]
    Units: micrograms/milliliter
    arithmetic mean (standard deviation)
        50 mg, n=34
    5.39 ( 3.03 )
        100 mg, n=30
    8.5 ( 5.45 )
        125 mg, n=1
    25.1 ( 5.92 )
        150 mg, n=12
    19.2 ( 10.8 )
        200 mg, n=15
    16 ( 10.7 )
        300 mg, n=15
    25.7 ( 14.9 )
    Notes
    [23] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated on-therapy AEs of special interest

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    End point title
    		 Number of participants with the indicated on-therapy AEs of special interest
    End point description
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. On-therapy events are defined as those AEs with an onset on or after the start date of study medication and up to 30 days after the last dose of study medication. Refer to the general AE/SAE module for a complete list of AEs and SAEs.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment plus 30 days post-treatment (average of 96.6 weeks)
    End point values
    		 Placebo Eltrombopag 50 mg
    Number of subjects analysed
    34 [24]
    64 [25]
    Units: Participants
        Any hepatobiliary events
    5
    12
        Any thromboembolic event
    1
    2
        Any renal event
    2
    8
        Any skin discoloration event
    0
    4
    Notes
    [24] - Safety Population
    [25] - Safety Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment AEs
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo tablets were administered to participants once daily for 6 months

    Reporting group title
    Eltrombopag 50 mg
    Reporting group description
    		 Participants initially received 50 milligram (mg) eltrombopag tablets orally once daily for 6 months. Intra-individual dose adjustments in a stepwise fashion to 100 mg, 200 mg or 300 mg were allowed based on the participants' platelet and bone marrow blast counts. For participants of East Asian heritage, a maximum dose of 150 mg was allowed. Stepwise dose adjustments from 50 mg to 100 mg or 150 mg were permitted for East Asian participants.

    Serious adverse events
    		 Placebo Eltrombopag 50 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 34 (67.65%)
    53 / 64 (82.81%)
         number of deaths (all causes)
    21
    40
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site granuloma
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mass
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 34 (2.94%)
    4 / 64 (6.25%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 4
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Reproductive system and breast disorders
    Balanitis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pericardial effusion
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic paroxysmal hemicrania
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    5 / 34 (14.71%)
    4 / 64 (6.25%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Increased tendency to bruise
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingival bleeding
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileal stenosis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatobiliary disorders
    Hepatitis acute
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal failure acute
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoporosis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fascial infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 34 (17.65%)
    5 / 64 (7.81%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Pneumonia fungal
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis Escherichia coli
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 34 (5.88%)
    4 / 64 (6.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Septic arthritis staphylococcal
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo Eltrombopag 50 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 34 (88.24%)
    58 / 64 (90.63%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    2 / 34 (5.88%)
    6 / 64 (9.38%)
         occurrences all number
    4
    15
    Haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    4
    Hypotension
         subjects affected / exposed
    1 / 34 (2.94%)
    4 / 64 (6.25%)
         occurrences all number
    1
    4
    Orthostatic hypotension
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 34 (11.76%)
    4 / 64 (6.25%)
         occurrences all number
    5
    4
    Catheter site haematoma
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Catheter site phlebitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Chest discomfort
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3
    Chills
         subjects affected / exposed
    0 / 34 (0.00%)
    4 / 64 (6.25%)
         occurrences all number
    0
    5
    Fatigue
         subjects affected / exposed
    6 / 34 (17.65%)
    15 / 64 (23.44%)
         occurrences all number
    6
    20
    General physical health deterioration
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Injection site extravasation
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Oedema
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 64 (4.69%)
         occurrences all number
    1
    3
    Oedema peripheral
         subjects affected / exposed
    5 / 34 (14.71%)
    9 / 64 (14.06%)
         occurrences all number
    5
    11
    Pain
         subjects affected / exposed
    2 / 34 (5.88%)
    3 / 64 (4.69%)
         occurrences all number
    2
    3
    Pyrexia
         subjects affected / exposed
    9 / 34 (26.47%)
    19 / 64 (29.69%)
         occurrences all number
    24
    28
    Suprapubic pain
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Scrotal pain
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    2 / 34 (5.88%)
    8 / 64 (12.50%)
         occurrences all number
    2
    9
    Dyspnoea
         subjects affected / exposed
    4 / 34 (11.76%)
    5 / 64 (7.81%)
         occurrences all number
    6
    5
    Dyspnoea exertional
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    3
    0
    Epistaxis
         subjects affected / exposed
    9 / 34 (26.47%)
    10 / 64 (15.63%)
         occurrences all number
    16
    15
    Haemoptysis
         subjects affected / exposed
    2 / 34 (5.88%)
    3 / 64 (4.69%)
         occurrences all number
    2
    3
    Nasal obstruction
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    0 / 34 (0.00%)
    5 / 64 (7.81%)
         occurrences all number
    0
    6
    Pleural effusion
         subjects affected / exposed
    2 / 34 (5.88%)
    3 / 64 (4.69%)
         occurrences all number
    2
    3
    Productive cough
         subjects affected / exposed
    2 / 34 (5.88%)
    3 / 64 (4.69%)
         occurrences all number
    3
    3
    Pulmonary congestion
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    3 / 34 (8.82%)
    2 / 64 (3.13%)
         occurrences all number
    4
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 64 (3.13%)
         occurrences all number
    2
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    Blood albumin decreased
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    5
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Blood bicarbonate decreased
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    Blood potassium decreased
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Blood urea increased
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    Blood urine present
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 34 (2.94%)
    4 / 64 (6.25%)
         occurrences all number
    1
    4
    White blood cell count
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Eye contusion
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Periorbital contusion
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Transfusion reaction
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Arrhythmia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Atrioventricular block
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Cardiomegaly
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Palpitations
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 64 (4.69%)
         occurrences all number
    1
    3
    Tachycardia
         subjects affected / exposed
    3 / 34 (8.82%)
    0 / 64 (0.00%)
         occurrences all number
    4
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 34 (2.94%)
    9 / 64 (14.06%)
         occurrences all number
    1
    10
    Dysgeusia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    2 / 34 (5.88%)
    8 / 64 (12.50%)
         occurrences all number
    2
    8
    Hypoaesthesia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Somnolence
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 34 (14.71%)
    6 / 64 (9.38%)
         occurrences all number
    5
    19
    Coagulopathy
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Haemorrhagic disorder
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Leukocytosis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Leukopenia
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    Lymphopenia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Neutropenia
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 64 (3.13%)
         occurrences all number
    2
    2
    Thrombocytopenia
         subjects affected / exposed
    1 / 34 (2.94%)
    4 / 64 (6.25%)
         occurrences all number
    1
    16
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3
    Conjunctivitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain
         subjects affected / exposed
    2 / 34 (5.88%)
    6 / 64 (9.38%)
         occurrences all number
    2
    6
    Abdominal pain upper
         subjects affected / exposed
    1 / 34 (2.94%)
    4 / 64 (6.25%)
         occurrences all number
    1
    4
    Constipation
         subjects affected / exposed
    3 / 34 (8.82%)
    10 / 64 (15.63%)
         occurrences all number
    3
    10
    Diarrhoea
         subjects affected / exposed
    6 / 34 (17.65%)
    18 / 64 (28.13%)
         occurrences all number
    8
    24
    Diverticulum
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Dry mouth
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    2 / 34 (5.88%)
    4 / 64 (6.25%)
         occurrences all number
    2
    4
    Epigastric discomfort
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    3
    0
    Flatulence
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Gastric ulcer
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Gingival bleeding
         subjects affected / exposed
    1 / 34 (2.94%)
    5 / 64 (7.81%)
         occurrences all number
    1
    5
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3
    Haemorrhoids
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3
    Lip swelling
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Melaena
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Mouth ulceration
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Nausea
         subjects affected / exposed
    5 / 34 (14.71%)
    20 / 64 (31.25%)
         occurrences all number
    5
    24
    Proctalgia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Rectal haemorrhage
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Stomatitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    Vomiting
         subjects affected / exposed
    1 / 34 (2.94%)
    12 / 64 (18.75%)
         occurrences all number
    1
    22
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 64 (3.13%)
         occurrences all number
    2
    2
    Ecchymosis
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Hyperhidrosis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Night sweats
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Petechiae
         subjects affected / exposed
    3 / 34 (8.82%)
    4 / 64 (6.25%)
         occurrences all number
    5
    5
    Pruritus
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 64 (4.69%)
         occurrences all number
    1
    3
    Rash
         subjects affected / exposed
    4 / 34 (11.76%)
    5 / 64 (7.81%)
         occurrences all number
    4
    6
    Skin discolouration
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3
    Urticaria
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 34 (8.82%)
    3 / 64 (4.69%)
         occurrences all number
    3
    4
    Back pain
         subjects affected / exposed
    8 / 34 (23.53%)
    8 / 64 (12.50%)
         occurrences all number
    8
    9
    Bone pain
         subjects affected / exposed
    1 / 34 (2.94%)
    5 / 64 (7.81%)
         occurrences all number
    1
    5
    Joint swelling
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 64 (3.13%)
         occurrences all number
    2
    2
    Musculoskeletal pain
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 64 (4.69%)
         occurrences all number
    1
    3
    Myalgia
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Pain in extremity
         subjects affected / exposed
    0 / 34 (0.00%)
    5 / 64 (7.81%)
         occurrences all number
    0
    5
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Candiduria
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Cellulitis
         subjects affected / exposed
    0 / 34 (0.00%)
    4 / 64 (6.25%)
         occurrences all number
    0
    6
    Cystitis
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    4
    Escherichia infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Fungal infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Herpes virus infection
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 64 (0.00%)
         occurrences all number
    2
    0
    Infection
         subjects affected / exposed
    2 / 34 (5.88%)
    4 / 64 (6.25%)
         occurrences all number
    2
    5
    Nasopharyngitis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Oral herpes
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal candidiasis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 64 (4.69%)
         occurrences all number
    2
    3
    Respiratory tract infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Sepsis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Sinusitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Stomatococcal infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Streptococcal infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    6
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 34 (5.88%)
    14 / 64 (21.88%)
         occurrences all number
    3
    16
    Fluid retention
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Gout
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Hyperkalaemia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 64 (0.00%)
         occurrences all number
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 34 (2.94%)
    6 / 64 (9.38%)
         occurrences all number
    1
    8
    Hypokalaemia
         subjects affected / exposed
    3 / 34 (8.82%)
    3 / 64 (4.69%)
         occurrences all number
    3
    3
    Hypomagnesaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Hyponatraemia
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 64 (3.13%)
         occurrences all number
    1
    2
    Hypophosphataemia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 64 (3.13%)
         occurrences all number
    0
    2
    Iron overload
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 64 (4.69%)
         occurrences all number
    0
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Jun 2010
    Amendment No. 02: Modified inclusion criteria to include de novo AML patients and bone marrow blasts of 10-19%. Updated liver chemistry stopping criteria. Added interim analysis for completers. Provided additional details regarding extension treatment periods.
    05 Mar 2012
    Amendment No. 03: Modified definitions of disease progression, baseline platelet count, platelet response, and evaluable subjects. Addition of an external adjudication committee. Updated details for the Primary Safety and Efficacy Analysis (previously Interim Analysis). Included optional collection of genetic mutations information. Clarifications and corrections to existing language throughout, including clarification to planned subject randomization numbers and planned PK analyses.
    25 Oct 2012
    Amendment No. 04: Modified to allow continued access to eltrombopag for ongoing subjects in Extension Period 3. The amendment applied only to 3 ongoing subjects at the time that the amendment was issued.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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