Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 74 of 141 for:    MPL

Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP) (PETIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00908037
Recruitment Status : Completed
First Posted : May 25, 2009
Results First Posted : October 31, 2014
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Purpura, Thrombocytopaenic, Idiopathic
Interventions Drug: eltrombopag
Drug: Placebo
Enrollment 82
Recruitment Details Pediatric participants (par.) 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 Details 15 par. were randomized to a 24-Week (Wk) Open-Label (OL) eltrombopag Dose-Finding period (pd) (Part 1) then did not continue. 67 par. were randomized to a 7-Wk Double-Blind placebo-controlled pd (Part 2), followed by a 24-Wk OL eltrombopag-only pd (Part 2/3) and a 4-Wk Follow-Up pd.
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3 Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open- Label Period) Cohort 3
Hide Arm/Group Description Participants aged between 12 and 17 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks. Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks. Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks. Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Period Title: Part1 (24 Week Dose-Finding Period)
Started 5 5 5 0 0 0 0 0 0 0 0 0
Completed 5 [1] 5 [1] 5 [1] 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
[1]
Participants who completed Part 1 did not enroll in Parts 2 or 2/3
Period Title: Part 2 (7 Week Randomized Period)
Started 0 0 0 8 16 9 19 5 10 0 0 0
Completed 0 0 0 7 13 9 15 5 5 0 0 0
Not Completed 0 0 0 1 3 0 4 0 5 0 0 0
Reason Not Completed
Protocol Violation             0             0             0             0             1             0             3             0             1             0             0             0
Lost to Follow-up             0             0             0             0             2             0             0             0             4             0             0             0
Withdrawal by parent/ guardian             0             0             0             1             0             0             1             0             0             0             0             0
Period Title: Part 2/3(Eltrombopag Open-Label Period)
Started 0 0 0 0 0 0 0 0 0 24 28 [1] 15
Completed 0 0 0 0 0 0 0 0 0 21 24 [1] 12
Not Completed 0 0 0 0 0 0 0 0 0 3 4 3
Reason Not Completed
Lack of Efficacy             0             0             0             0             0             0             0             0             0             0             0             1
Lost to Follow-up             0             0             0             0             0             0             0             0             0             1             0             2
Withdrawal by parent/guardian             0             0             0             0             0             0             0             0             0             1             0             0
Adverse Event             0             0             0             0             0             0             0             0             0             0             2             0
Physician Decision             0             0             0             0             0             0             0             0             0             1             0             0
Randomized but did not receive treatment             0             0             0             0             0             0             0             0             0             0             2             0
[1]
Two participants were randomized but did not receive treatment.
Arm/Group Title Part 1 Eltrombopag Dose-Finding Period Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag Total
Hide Arm/Group Description Participants (par) aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 24 weeks. The starting dose for Cohort 1 was 25 mg, and par of East Asian ancestry received 12.5mg QD. For Cohort 2 starting dose was based on the body weight. Par with a bodyweight of <27 kg received 12.5 mg QD, par with a body weight of >=27 kg received 25 mg QD; par of East Asian ancestry with a body weight <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 0.7 mg/kg QD and 0.5 mg/kg/day for par of East Asian ancestry and the dose calculations were based on the body weight. The maximum dose allowed for all Cohorts was 75mg daily. For all par, individual dose titration was allowed based upon platelet response. Par aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks. All par completing Part 2 of the study received an OL treatment of eltrombopag administered as a tablet in Part 2/3. Par who received placebo in Part 2 received 24 weeks of OL treatment of eltrombopag in Part 2/3 starting at 37.5 mg QD up to Week 31 of the study. The maximum dose allowed was 75 mg daily. All par enrolled in the study underwent individual dose titration based upon platelet response. Par aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. All par completing Part 2 of the study received an OL treatment of eltrombopag administered as a tablet in Part 2/3. Par who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All par enrolled in the study underwent individual dose titration based upon platelet response. Par aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks. All par completing Part 2 of the study received an OL treatment of eltrombopag administered as a tablet in Part 2/3. Par with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Par who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Par with a body weight of &lt;=27 kg received 25 mg QD and par with a body weight of &gt;=27 kg QD received 50 mg QD. The maximum dose allowed was 75 mg daily. All par enrolled in the study underwent individual dose titration based upon platelet response. Par aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, par with a weight of &lt;27 kg received 25 mg QD and par with a weight of &gt;=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of &lt;27 kg received 12.5 mg QD and par with a weight of &gt;=27 kg received 25 mg QD. All par completing Part 2 of the study received an OL treatment of eltrombopag administered as a tablet in Part 2/3. Par with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Par who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All par enrolled in the study underwent individual dose titration based upon platelet response. Par aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks. All par completing Part 2 of the study received an OL treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Par who received placebo in Part 2 received 24 weeks of OL treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Par of East Asian ancestry received 0.8 mg/kg/day. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response. Par aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Par of East Asian ancestry began at 0.8 mg/kg/day. All par completing Part 2 of the study received an OL treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Par who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All par enrolled in the study underwent individual dose titration based upon platelet response. Total of all reporting groups
Overall Number of Baseline Participants 15 8 16 9 19 5 10 82
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 8 participants 16 participants 9 participants 19 participants 5 participants 10 participants 82 participants
9.1  (4.61) 14.6  (1.69) 13.7  (1.58) 8.6  (2.24) 8.2  (1.87) 3.6  (1.34) 3.3  (1.34) 9.3  (4.49)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 8 participants 16 participants 9 participants 19 participants 5 participants 10 participants 82 participants
Female
8
  53.3%
3
  37.5%
8
  50.0%
8
  88.9%
14
  73.7%
2
  40.0%
5
  50.0%
48
  58.5%
Male
7
  46.7%
5
  62.5%
8
  50.0%
1
  11.1%
5
  26.3%
3
  60.0%
5
  50.0%
34
  41.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 8 participants 16 participants 9 participants 19 participants 5 participants 10 participants 82 participants
African American/African Heritage 2 0 0 0 1 0 0 3
Asian – Japanese/East Asian Heritage 2 1 0 1 1 0 1 6
White – White/Caucasian/European 9 7 14 8 17 5 7 67
Unknown 1 0 0 0 0 0 0 1
White - Arabic/North African Heritage 0 0 1 0 0 0 1 2
Mixed Race 1 0 1 0 0 0 1 3
1.Primary Outcome
Title Percentage of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) at Least Once, Between Day 8 and Day 43 (Weeks 1 to 6) of the Randomized Period of the Study (Part 2)
Hide Description Participants who achieved a platelet count >=50 Gi/L at least once between Day 8 and Day 43 (first 6 weeks of Part 2) in the absense of rescue treatment were reported. A 95% confidence interval was calculated by the exact binomial method.
Time Frame From Day 8 up to Day 43 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all enrolled participants during Part 2. The ITT Population was the primary population used for assessing efficacy. Only evaluable participants were considered for analysis where participants with a Baseline platelet count >10Gi/L was considered as evaluable.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 17 5 10
Measure Type: Number
Unit of Measure: Percentage of Participants
0 62.5 33.3 63.2 80.0 60.0
2.Secondary Outcome
Title Percentage of Participants Achieving Platelet Counts >=50Gi/L During Treatment With Eltrombopag in >= 60% of Assessments Between Day 15 and Day 43 (Weeks 2 Through 6) of the Randomized Treatment Period (Part 2)
Hide Description Sustained platelet response between the treatment groups was assessed by determining the number of participants who achieved a platelet count >=50 Gi/L during treatment with eltrombopag in >= 60% of assessments between Day 15 and Day 43 in the absence of rescue treatment were reported here.
Time Frame Between Day 15 and Day 43 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population, only those participants enrolled in Part 2 of this study were analyzed.
Arm/Group Title Part 2 (Randomized Period) -Placebo Part 2 (Randomized Period) - Eltrombopag
Hide Arm/Group Description:
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag matching placebo for 7 weeks.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 7 weeks. The starting dose for Cohort 1 was 37.5 mg QD. For Cohort 2, starting dose was based on the body weight. Par with a body weight of <27 kg received 25 mg QD, and par with a body weight of >=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 1.5 mg/kg QD and 0.8 mg/kg/day for par of East Asian ancestry. The maximum dose allowed was 2mg/kg and could not exceed 75 mg daily. For all par, individual dose titration was allowed based upon platelet response.
Overall Number of Participants Analyzed 22 45
Measure Type: Number
Unit of Measure: Percentage of Participants
0 35.6
3.Secondary Outcome
Title Weighted Mean Platelet Count
Hide Description The weighted mean platelet count is defined as the area under the platelet-time curve divided by the duration of the treatment (12 weeks). Based on the Analysis of Covariance (ANCOVA) model, the weighted mean platelet count is the sum of the Baseline count plus the age cohort plus the treatment. Baseline was defined as the platelet count taken on Day 1 or within 48 hours prior to the first dose of treatment.
Time Frame Baseline and Day 43 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants during Part 2 with a value at baseline and post-baseline were considered for analysis
Arm/Group Title Part 2 (Randomized Period) -Placebo Part 2 (Randomized Period) - Eltrombopag
Hide Arm/Group Description:
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag matching placebo for 7 weeks.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 7 weeks. The starting dose for Cohort 1 was 37.5 mg QD. For Cohort 2, starting dose was based on the body weight. Par with a body weight of <27 kg received 25 mg QD, and par with a body weight of >=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 1.5 mg/kg QD and 0.8 mg/kg/day for par of East Asian ancestry. The maximum dose allowed was 2mg/kg and could not exceed 75 mg daily. For all par, individual dose titration was allowed based upon platelet response.
Overall Number of Participants Analyzed 21 43
Mean (Standard Deviation)
Unit of Measure: Gi/L
Baseline 12.2  (8.59) 15.5  (8.03)
Day 43 30.5  (24.98) 68  (56.78)
4.Secondary Outcome
Title Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1.
Hide Description The percentage of participants achieving platelet counts >=50Gi/L at least once at any time during the 24 weeks of eltrombopag treatment were reported.
Time Frame From Day 1 of treatment up to Week 24 of Part 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population only those participants enrolled during Part 1 were analyzed.
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Measure Type: Number
Unit of Measure: Percentage of Participants
80 80 60
5.Secondary Outcome
Title Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/ 3.
Hide Description The percentage of participants achieving platelet counts >=50Gi/L at least once at any time during the 24 weeks of eltrombopag treatment during Part 2/3 of the study were reported. Participants randmoized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.
Time Frame Part 2/3 up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only evaluable participants were included for this analysis, where participants with a baseline platelet count >10 Gi/L was considered as evaluable.
Arm/Group Title Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open-Label Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Particpiants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Particpiants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of &lt;=27 kg received 25 mg QD and participants with a body weight of &gt;=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Particpiants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 26 15
Measure Type: Number
Unit of Measure: Percentage of Participants
75.0 82.1 86.7
6.Secondary Outcome
Title Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3.
Hide Description The area under the concentration-time curve over the dosing interval (AUC0-t) data was collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. Doses were normalized to 50mg for comparison. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. 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. From the final model, a single value of AUC(0-t) was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.
Time Frame From Day 1 of treatment up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.
Arm/Group Title Eltrombopag Cohort 1- 12-17 Years Eltrombopag Cohort 2 - 6-11 Years Eltrombopag Cohort 3 - 1-5 Years
Hide Arm/Group Description:
Participants (par) aged between 12 and 17 years received eltrombopag administered as a tablet for a total of 24 weeks. Par in Part 1 received an Open-Label (OL) treatment (trt) starting at 25 milligrams (mg) once daily (QD) for 24 weeks. Par of East Asian ancestry began at 12.5mg QD. Par randomized to eltrombopag in Part 2 received eltrombopag for 7 weeks starting at 37.5mg QD. All par completing Part 2 received an OL trt of eltrombopag in Part 2/3. Par who received 7 weeks of eltrombopag in Part 2 received an additional 17 weeks of trt to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. Par who received placebo Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 starting at 37.5 mg QD up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 6 and 11 years received eltrombopag administered as a tablet or dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par weighing <27 kilograms (kg) started at 12.5mg QD and par weighing >=27kg started at 25mg QD. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par weighing <27kg started at 25mg QD and par weighing >=27kg started at 50mg QD. Par of East Asian ancestry weighing <27kg began at 12.5mg QD and those >=27kg began at 25mg QD. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 1 and 5 years received eltrombopag administered as a dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par starting dose was 0.7mg/kg QD, par of East Asian ancestry began at 0.5mg/kg/day. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par starting dose was 1.5mg/kg QD, par of East Asian ancestry weighing began at 0.8 mg/kg/day. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 29 30 19
Geometric Mean (95% Confidence Interval)
Unit of Measure: Microgram*hour per milliliter (ug*h/mL)
101
(87.1 to 117)
132
(114 to 152)
142
(117 to 173)
7.Secondary Outcome
Title Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3.
Hide Description The maximum observed concentration (Cmax) and the concentration at the end of the dosing interval (Ct) data were collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. Doses were normalized to 50mg for comparison. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. From the final model, a single value of Cmax and Ct were estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.
Time Frame From Day 1 of treatment up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.
Arm/Group Title Eltrombopag Cohort 1- 12-17 Years Eltrombopag Cohort 2 - 6-11 Years Eltrombopag Cohort 3 - 1-5 Years
Hide Arm/Group Description:
Participants (par) aged between 12 and 17 years received eltrombopag administered as a tablet for a total of 24 weeks. Par in Part 1 received an Open-Label (OL) treatment (trt) starting at 25 milligrams (mg) once daily (QD) for 24 weeks. Par of East Asian ancestry began at 12.5mg QD. Par randomized to eltrombopag in Part 2 received eltrombopag for 7 weeks starting at 37.5mg QD. All par completing Part 2 received an OL trt of eltrombopag in Part 2/3. Par who received 7 weeks of eltrombopag in Part 2 received an additional 17 weeks of trt to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. Par who received placebo Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 starting at 37.5 mg QD up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 6 and 11 years received eltrombopag administered as a tablet or dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par weighing <27 kilograms (kg) started at 12.5mg QD and par weighing >=27kg started at 25mg QD. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par weighing <27kg started at 25mg QD and par weighing >=27kg started at 50mg QD. Par of East Asian ancestry weighing <27kg began at 12.5mg QD and those >=27kg began at 25mg QD. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 1 and 5 years received eltrombopag administered as a dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par starting dose was 0.7mg/kg QD, par of East Asian ancestry began at 0.5mg/kg/day. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par starting dose was 1.5mg/kg QD, par of East Asian ancestry weighing began at 0.8 mg/kg/day. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 29 30 19
Geometric Mean (95% Confidence Interval)
Unit of Measure: micrograms per milliliter (ug/mL)
Cmax
6.65
(5.87 to 7.53)
9.19
(8.18 to 10.3)
10.7
(9.24 to 12.5)
Ct
2.42
(1.97 to 2.98)
2.95
(2.41 to 3.60)
2.91
(2.14 to 3.96)
8.Secondary Outcome
Title Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3
Hide Description The time to maximum concentration (tmax) was collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. From the final model, a single value of tmax was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.
Time Frame From Day 1 of treatment up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.
Arm/Group Title Eltrombopag Cohort 1- 12-17 Years Eltrombopag Cohort 2 - 6-11 Years Eltrombopag Cohort 3 - 1-5 Years
Hide Arm/Group Description:
Participants (par) aged between 12 and 17 years received eltrombopag administered as a tablet for a total of 24 weeks. Par in Part 1 received an Open-Label (OL) treatment (trt) starting at 25 milligrams (mg) once daily (QD) for 24 weeks. Par of East Asian ancestry began at 12.5mg QD. Par randomized to eltrombopag in Part 2 received eltrombopag for 7 weeks starting at 37.5mg QD. All par completing Part 2 received an OL trt of eltrombopag in Part 2/3. Par who received 7 weeks of eltrombopag in Part 2 received an additional 17 weeks of trt to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. Par who received placebo Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 starting at 37.5 mg QD up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 6 and 11 years received eltrombopag administered as a tablet or dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par weighing <27 kilograms (kg) started at 12.5mg QD and par weighing >=27kg started at 25mg QD. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par weighing <27kg started at 25mg QD and par weighing >=27kg started at 50mg QD. Par of East Asian ancestry weighing <27kg began at 12.5mg QD and those >=27kg began at 25mg QD. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 1 and 5 years received eltrombopag administered as a dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par starting dose was 0.7mg/kg QD, par of East Asian ancestry began at 0.5mg/kg/day. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par starting dose was 1.5mg/kg QD, par of East Asian ancestry weighing began at 0.8 mg/kg/day. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 29 30 19
Median (Full Range)
Unit of Measure: hour (hr)
4.0
(2.0 to 6.0)
4.0
(2.0 to 6.0)
2.0
(2.0 to 4.0)
9.Secondary Outcome
Title Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3
Hide Description The apparent plasma clearance following oral dosing of eltrombopag (CL/F) was collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. From the final model, a single value of CL/F was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.
Time Frame From Day 1 of treatment up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.
Arm/Group Title Eltrombopag Cohort 1- 12-17 Years Eltrombopag Cohort 2 - 6-11 Years Eltrombopag Cohort 3 - 1-5 Years
Hide Arm/Group Description:
Participants (par) aged between 12 and 17 years received eltrombopag administered as a tablet for a total of 24 weeks. Par in Part 1 received an Open-Label (OL) treatment (trt) starting at 25 milligrams (mg) once daily (QD) for 24 weeks. Par of East Asian ancestry began at 12.5mg QD. Par randomized to eltrombopag in Part 2 received eltrombopag for 7 weeks starting at 37.5mg QD. All par completing Part 2 received an OL trt of eltrombopag in Part 2/3. Par who received 7 weeks of eltrombopag in Part 2 received an additional 17 weeks of trt to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. Par who received placebo Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 starting at 37.5 mg QD up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 6 and 11 years received eltrombopag administered as a tablet or dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par weighing <27 kilograms (kg) started at 12.5mg QD and par weighing >=27kg started at 25mg QD. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par weighing <27kg started at 25mg QD and par weighing >=27kg started at 50mg QD. Par of East Asian ancestry weighing <27kg began at 12.5mg QD and those >=27kg began at 25mg QD. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Par aged between 1 and 5 years received eltrombopag administered as a dry powder for oral suspension for a total of 24 weeks. Par in Part 1 received an OL trt based on body weight for 24 weeks. Par starting dose was 0.7mg/kg QD, par of East Asian ancestry began at 0.5mg/kg/day. Par randomized to eltrombopag in Part 2 received trt based on body weight for 7 weeks. Par starting dose was 1.5mg/kg QD, par of East Asian ancestry weighing began at 0.8 mg/kg/day. Par who received 7 weeks of eltrombopag in Part 2 continued the same dose in Part 2/3 for an additional 17 weeks of trt to complete a total of 24 weeks. Par who received placebo in Part 2, received 24 weeks of trt of eltrombopag in Part 2/3 using the same dosing guidelines as Part 2 up to Week 31 of the study. The maximum dose allowed was 75mg daily. All par underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 29 30 19
Geometric Mean (95% Confidence Interval)
Unit of Measure: liter per hour (L/hr)
0.50
(0.43 to 0.57)
0.38
(0.33 to 0.44)
0.25
(0.20 to 0.30)
10.Secondary Outcome
Title Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the 7 Weeks of Eltrombopag Treatment in Part 2
Hide Description The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L in the absence of rescue treatment was calculated and summarized during the 24 weeks of eltrombopag treatment in 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 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. Excludes periods from initiation of rescue medication until platelet count falls to below 50Gi/L, irrespective of platelet count
Time Frame From Baseline through Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population, only those participants enrolled in Part 2 were analyzed. The number of participants used to compute the summary statistics reflect the ITT poplation through out the analyses during Part 2.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 19 5 10
Median (Full Range)
Unit of Measure: Weeks
0.0
(0 to 0)
1.0
(0 to 5)
0.0
(0 to 2)
2.0
(0 to 6)
1.0
(0 to 2)
1.0
(0 to 6)
11.Secondary Outcome
Title Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the 24 Weeks of Eltrombopag Treatment in Part 2/ 3
Hide Description The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L in the absence of rescue treatment was calculated and summarized during the 24 weeks of eltrombopag treatment in Part 2/3. 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. Participants randmoized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.
Time Frame From Baseline up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population only those participants enrolled in Part 2/3 were analyzed. The number of participants used to compute the summary statistics reflect the ITT poplation through out the analyses during Part 2/3.
Arm/Group Title Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open-Label Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 28 15
Median (Full Range)
Unit of Measure: Weeks
2.0
(0 to 23)
8.0
(0 to 24)
4.0
(0 to 24)
12.Secondary Outcome
Title Percentage of Participants Who Reduced or Discontinued Baseline Concomitant Idiopathic Thrombocytopenic Purpura (ITP) Medications During the 24 Weeks of Eltrombopag Treatment During Part 1.
Hide Description The participants who discontinued (dis) or had a sustained reduction (red) of a Baseline (BL) ITP medication for at least one day during the period of Day 1 of Part 1 to the last dose of study medication +1 day are reported. The denominator is the number of subjects taking an ITP medication at baseline. For participants in Part 1, Baseline is defined as Day 1 of Part 1. A sustained reduction is defined as reduction for 4 weeks or more. An attempted red or dis is a decrease in the dose or frequency from the BL dose or frequency of an ITP medication for at least one day during the period Part 1 Day 1 to the last dose of study medication + 1 day.
Time Frame From Baseline up to Week 24+ 1 day of Part 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population, only those participants enrolled during Part 1 were analyzed.
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Measure Type: Number
Unit of Measure: Percentage of Participants
Taking an ITP medication at BL 0 20.0 0
Attempted red or dis 0 100.0 0
Permanent red or dis of all BL ITP mediation 0 100.0 0
Permanent red or dis at least 1 BL ITP medcation 0 100.0 0
13.Secondary Outcome
Title Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/ 3
Hide Description Participants who discontinued (dis) or had a sustained reduction (red) of a Baseline (BL) ITP medication for at least one day during the period of Day 1 of Part 2/3 to the last dose of study medication +1 day are reported. The denominator is the number of subjects taking an ITP medication at baseline. For participants randomized to placebo in Part 2, BL is defined as Week 7 of Part 2. For participants randomized to eltrombopag in Part 2, BL is defined as Day 1 of Part 2. A sustained reduction is defined as reduction for 4 weeks or more. An attempted reduction or discontinuation is a decrease in the dose or frequency from the BL dose or frequency of an ITP medication for at least one day during the period Part 2/3 Day 1 to the last dose of study medication + 1 day.
Time Frame From Baseline to the end of treatment up to Week 31 + 1 day of Part 2/3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population, only those participants enrolled during Part 2/3 were analyzed.
Arm/Group Title Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open-Label Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 28 15
Measure Type: Number
Unit of Measure: Percentage of Participants
Taking an ITP medication at BL 25.0 17.9 13.3
Attempted red or dis 66.7 20.0 100.0
Permanent (perm) dis of all BL ITP medication(med) 16.7 20.0 50.0
Perm dis at least 1 BL ITP med 33.3 20.0 50.0
Perm dis all BL ITP med taken prior to Part 2/3 0 40.0 0
14.Secondary Outcome
Title Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3
Hide 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. For particpants randomized to placebo in Part 2, Baseline is defined as Week 7 of Part 2. For participants randomized to eltrombopag in Part 2, Baseline is defined as Day 1 of Part 2. Participants randmoized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.
Time Frame From Baseline to the end of treatment up to Week 31 + 1 day of Part2/3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population, only those participants enrolled during Part 2/3 were analyzed.
Arm/Group Title Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open-Label Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 28 15
Measure Type: Number
Unit of Measure: Participants
New ITP Medication 8 4 4
Increase concomitant ITP medication from Baseline 1 0 0
Platelet transfusion 0 0 0
Splenectomy 0 0 0
15.Secondary Outcome
Title Kids’ ITP Tool (KIT) Questionnaire Total Score at Baseline, Week 6, Week 12, and Week 24 as Assessed Using the KIT Questionnaire During the Dose Finding Period, Part 1
Hide Description The KIT questionnaire measures the impact on the quality of life determined by the participant and the guardian by self reported outcomes at Baseline or the Screening Visit, after 6 weeks of treatment, after 12 weeks of treatment and at the end of treatment or withdrawal from the study. The KIT total score is calculated from the scores of each of the individual questions from Q1 – Q26 (excluding any answer that is ‘Not applicable’). The code list used for the individual question scores is: 1 = never, 2 = seldom, 3 = sometimes, 4 = often, 5 = always and 9 = not applicable. The range of values the total score can take is 0 (worst) to 100 (best). For subjects under the age of six, the family questionnaire (parental proxy) has been used.
Time Frame Baseline, Week 6, Week 12, and Week 24 of Part 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Mean (Standard Deviation)
Unit of Measure: Score on scale
Baseline, n=5, 5, 5 73.18  (15.743) 53.95  (16.534) 74.80  (17.199)
Week 6, n=4, 5, 5 82.84  (9.131) 61.57  (13.664) 71.54  (14.798)
Week 12, n=4, 4, 4 84.14  (11.712) 66.43  (12.349) 65.58  (17.887)
Week 24, n= 3, 4, 3 76.38  (20.228) 82.50  (15.995) 78.87  (12.056)
16.Secondary Outcome
Title Kids’ ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2
Hide Description The KIT questionnaire measures the impact on the quality of life determined by the participant and the guardian by self reported outcomes at Baseline or the Screening Visit, after 6 weeks of treatment or withdrawal from the study. The KIT total score is calculated from the scores of each of the individual questions from Q1 – Q26 (excluding any answer that is ‘Not applicable’). The code list used for the individual question scores is: 1 = never, 2 = seldom, 3 = sometimes, 4 = often, 5 = always and 9 = not applicable. The range of values the total score can take is 0 (worst) to 100 (best). For subjects under the age of six, the family questionnaire (parental proxy) has been used.
Time Frame Baseline and Week 6 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 19 5 10
Mean (Standard Deviation)
Unit of Measure: Score on scale
Baseline, n=6, 11, 9, 10, 2, 8 83.94  (8.674) 76.84  (15.049) 71.05  (19.581) 66.36  (17.321) 82.61  (7.686) 78.23  (9.575)
Week 6, n= 8,11,7,13, 5, 9 79.46  (10.971) 79.46  (13.899) 74.65  (20.968) 80.16  (13.776) 88.01  (3.333) 80.85  (15.082)
17.Secondary Outcome
Title Kids’ ITP Tools (KIT) Questionnaire Total Score at Baseline, Week, 6, Week 12, and End of Treatment Visit as Assessed Using the KIT Questionnaire During the Eltrombopag Open-Label Period, Part 2/3
Hide Description The KIT questionnaire measures the impact on the quality of life determined by the participant and the guardian by self reported outcomes at Baseline or the Screening Visit, after 6 weeks of treatment, after 12 weeks of treatment and at the end of treatment or withdrawal from the study. The KIT total score is calculated from the scores of each of the individual questions from Q1 – Q26 (excluding any answer that is ‘Not applicable’). The code list used for the individual question scores is: 1=never, 2=seldom, 3=sometimes, 4=often, 5=always and 9=not applicable. The range of values the total score can take is 0 (worst) to 100 (best). For subjects under the age of six, the family questionnaire (parental proxy) has been used.
Time Frame From Baseline to end of treatment up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
Arm/Group Title Part 2/3 (Eltrombopag Period) Cohort 1 Part 2/3 (Eltrombopag Period) Cohort 2 Part 2/3 (Eltrombopag Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 28 15
Mean (Standard Deviation)
Unit of Measure: Score on scale
Baseline, n=17, 18, 10 79.34  (13.315) 70.59  (16.237) 79.10  (9.016)
Week 6, n=11, 13, 9 79.46  (13.899) 80.16  (13.776) 80.85  (15.082)
Week 12, n=9, 7, 2 84.25  (7.531) 76.48  (19.948) 88.10  (11.166)
Week 24, n=17, 11, 8 82.16  (16.926) 83.93  (13.327) 77.93  (22.971)
18.Secondary Outcome
Title Number of Participants With Any Bleeding, no Clinically Significant Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale During Part 2
Hide 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=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. For participants randomized to Placebo in Part 2, Baseline defined as Week 7 of Part 2. For participants randomized to Eltrombopag in Part 2, Baseline defined as Day 1 of Part 2.
Time Frame From Baseline through Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 19 5 10
Measure Type: Number
Unit of Measure: Participants
Baseline, Grades 1-4, n=8, 16, 9, 19, 5, 10 6 16 7 11 5 8
Baseline, Grades 0-1, n=8, 16, 9, 19, 5, 10 6 13 6 17 4 6
Baseline, Grades 2-4, n=8, 16, 9, 19, 5, 10 2 3 3 2 1 4
Week 1, Grades 1-4, n=8, 16, 9, 17, 5, 10 7 9 6 7 3 7
Week 1, Grades 0-1, n=8, 16, 9, 17, 5, 10 3 14 6 17 5 5
Week 1, Grades 2-4, n=8, 16, 9, 17, 5, 10 5 2 3 0 0 5
Week 2, Grades 1-4, n=8, 16, 9, 17, 5, 10 7 11 6 6 2 5
Week 2, Grades 0-1, n=8, 16, 9, 17, 5, 10 5 13 7 16 3 7
Week 2, Grades 2-4, n=8, 16, 9, 17, 5, 10 3 3 2 1 2 3
Week 3, Grades 1-4, n=8, 16, 9, 16, 5, 9 6 10 7 6 2 5
Week 3, Grades 0-1, n=8, 16, 9, 16, 5, 9 5 14 7 14 3 7
Week 3, Grades 2-4, n=8, 16, 9, 16, 5, 9 3 2 2 2 2 2
Week 4, Grades 1-4, n=8, 16, 9, 17, 5, 9 6 7 7 7 2 6
Week 4, Grades 0-1, n=8, 16, 9, 17, 5, 9 6 16 8 17 3 7
Week 4, Grades 2-4, n=8, 16, 9, 17, 5, 9 2 0 1 0 2 2
Week 5, Grades 1-4, n=8, 16, 9, 16, 5, 9 6 8 7 3 4 5
Week 5, Grades 0-1, n=8, 16, 9, 16, 5, 9 4 14 8 16 4 8
Week 5, Grades 2-4, n=8, 16, 9, 16, 5, 9 4 2 1 0 1 1
Week 6, Grades 1-4, n=8, 16, 9, 17, 5, 9 5 2 7 4 4 4
Week 6, Grades 0-1, n=8, 16, 9, 17, 5, 9 7 16 7 16 4 9
Week 6, Grades 2-4, n=8, 16, 9, 17, 5, 9 1 0 2 1 1 0
Week 7, Grades 1-4, n=8, 16, 9, 17, 5, 9 7 5 7 5 4 4
Week 7, Grades 0-1, n=8, 16, 9, 17, 5, 9 4 15 8 16 3 7
Week 7, Grades 2-4, n=8, 16, 9, 17, 5, 9 4 1 1 1 2 2
19.Secondary Outcome
Title Number of Participants With Any Bleeding, no Clinically Significant Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale During Part 2/3
Hide 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=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. For participants randomized to Placebo in Part 2, Baseline defined as Week 7 of Part 2. For participants randomized to Eltrombopag in Part 2, Baseline defined as Day 1 of Part 2.
Time Frame From Baseline of Part 2/3 through Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
Arm/Group Title Part 2/ 3 (Eltrombopag Period) Cohort 1 Part 2/3 (Eltrombopag Period) Cohort 2 Part 2/3 (Eltrombopag Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Particpiants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Particpiants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Particpiants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the studyat 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 28 15
Measure Type: Number
Unit of Measure: Participants
Baseline, Grades 1-4, n=24, 28, 15 23 18 12
Baseline, Grades 0-1, n=24, 28, 15 17 25 9
Baseline, Grades 2-4, n=24, 28, 15 7 3 6
Week 1, Grades 1-4, n=24, 26, 15 14 13 9
Week 1, Grades 0-1, n=24, 26, 15 20 24 9
Week 1, Grades 2-4, n=24, 26, 15 4 2 6
Week 2, Grades 1-4, n=24, 26, 14 15 12 8
Week 2, Grades 0-1, n=24, 26, 14 21 23 10
Week 2, Grades 2-4, n=24, 26, 14 3 3 4
Week 3, Grades 1-4, n=24, 25, 14 13 9 6
Week 3, Grades 0-1, n=24, 25, 14 21 23 12
Week 3, Grades 2-4, n=24, 25, 14 3 2 2
Week 4, Grades 1-4, n=24, 26, 13 10 11 8
Week 4, Grades 0-1, n=24, 26, 13 24 26 10
Week 4, Grades 2-4, n=24, 26, 13 0 0 3
Week 5, Grades 1-4, n=24, 24, 13 11 4 9
Week 5, Grades 0-1, n=24, 24, 13 21 24 12
Week 5, Grades 2-4, n=24, 24, 13 3 0 1
Week 6, Grades 1-4, n=23, 24, 12 6 6 4
Week 6, Grades 0-1, n=23, 24, 12 23 22 12
Week 6, Grades 2-4, n=23, 24, 12 0 2 0
Week 7, Grades 1-4, n=22, 25, 14 8 7 4
Week 7, Grades 0-1, n=22, 25, 14 20 24 12
Week 7, Grades 2-4, n=22, 25, 14 2 1 2
Week 8, Grades 1-4, n=19, 21, 11 10 6 5
Week 8, Grades 0-1, n=19, 21, 11 19 19 9
Week 8, Grades 2-4, n=19, 21, 11 0 2 2
Week 9, Grades 1-4, n=17, 16, 12 8 5 6
Week 9, Grades 0-1, n=17, 16, 12 13 16 10
Week 9, Grades 2-4, n=17, 16, 12 4 0 2
Week 10, Grades 1-4, n=16, 14, 11 5 5 7
Week 10, Grades 0-1, n=16, 14, 11 16 12 11
Week 10, Grades 2-4, n=16, 14, 11 0 2 0
Week 11, Grades 1-4, n=16, 15, 12 15 5 7
Week 11, Grades 0-1, n=16, 15, 12 16 13 10
Week 11, Grades 2-4, n=16, 15, 12 0 2 2
Week 12, Grades 1-4, n=19, 16, 9 6 7 4
Week 12, Grades 0-1, n=19, 16, 9 18 14 7
Week 12, Grades 2-4, n=19, 16, 9 1 2 2
Week 13, Grades 1-4, n=12, 14, 10 6 5 6
Week 13, Grades 0-1, n=12, 14, 10 12 13 10
Week 13, Grades 2-4, n=12, 14, 10 0 1 0
Week 14, Grades 1-4, n=15, 11, 17 3 2 3
Week 14, Grades 0-1, n=15, 11, 17 15 11 5
Week 14, Grades 2-4, n=15, 11, 17 0 0 2
Week 15, Grades 1-4, n=12, 14, 6 6 3 3
Week 15, Grades 0-1, n=12, 14, 6 10 14 5
Week 15, Grades 2-4, n=12, 14, 6 2 0 1
Week 16, Grades 1-4, n=17, 15, 9 7 8 4
Week 16, Grades 0-1, n=17, 15, 9 17 14 9
Week 16, Grades 2-4, n=17, 15, 9 0 1 0
Week 17, Grades 1-4, n=13, 11, 5 5 3 4
Week 17, Grades 0-1, n=13, 11, 5 13 11 5
Week 17, Grades 2-4, n=13, 11, 5 0 0 0
Week 18, Grades 1-4, n=16, 12 ,4 3 2 3
Week 18, Grades 0-1, n=16, 12 ,4 16 11 4
Week 18, Grades 2-4, n=16, 12 ,4 0 1 0
Week 19, Grades 1-4, n=14, 15, 7 3 4 1
Week 19, Grades 0-1, n=14, 15, 7 14 14 7
Week 19, Grades 2-4, n=14, 15, 7 0 1 0
Week 20, Grades 1-4, n=13, 13, 8 2 3 2
Week 20, Grades 0-1, n=13, 13, 8 13 13 6
Week 20, Grades 2-4, n=13, 13, 8 0 0 2
Week 21, Grades 1-4, n=4, 10, 3 1 0 0
Week 21, Grades 0-1, n=4, 10, 3 4 10 3
Week 21, Grades 2-4, n=4, 10, 3 0 0 0
Week 22, Grades 1-4, n=12,7, 5 2 2 2
Week 22 Grades 0-1, n=12,7, 5 12 6 5
Week 22 Grades 2-4, n=12,7, 5 0 1 0
Week 23, Grades 1-4, n=8, 7,6 1 1 2
Week 23, Grades 0-1, n=8, 7,6 8 7 6
Week 23, Grades 2-4, n=8, 7,6 0 0 0
Week 24, Grades 1-4, n=23, 24, 13 5 5 4
Week 24, Grades 0-1, n=23, 14, 13 21 24 12
Week 24, Grades 2-4, n=23, 14, 13 2 0 1
Follow Up Week 1, Grades 1-4, n=8, 5, 3 5 1 3
Follow Up Week 1, Grades 0-1, n=8, 5, 3 8 4 2
Follow Up Week 1, Grades 2-4, n=8, 5, 3 0 1 1
Follow Up Week 2, Grades 1-4, n=7, 7, 7 2 6 2
Follow Up Week 2, Grades 0-1, n=7, 7, 7 7 6 6
Follow Up Week 2, Grades 2-4, n=7, 7, 7 0 1 1
Follow Up Week 3, Grades 1-4, n=5, 5, 5 1 2 4
Follow Up Week 3, Grades 0-1, n=5, 5, 5 5 5 4
Follow Up Week 3, Grades 2-4, n=5, 5, 5 0 0 1
Follow Up Week 4, Grades 1-4, n=9, 14, 8 5 4 3
Follow Up Week 4, Grades 0-1, n=9, 14, 8 8 13 7
Follow Up Week 4, Grades 2-4, n=9, 14, 8 1 1 1
Any Follow Up Visit, Grades 1, n=15, 18, 10 7 10 5
Any Follow Up Visit, Grades 0-1, n=15, 18, 10 15 18 9
Any Follow Up Visit, Grades 2-4, n=15, 18, 10 1 3 3
20.Secondary Outcome
Title Number of Participants With the Indicated Clinical Chemistry Parameter Falling Outside of the Reference Range Any Time Post-Baseline During Part 1, Part 2, and Part 2/3
Hide Description Clinical chemistry parameters included: aspartate amino transferase (AST, reference range [RR]: 0-38 International Units per Liter [IU/L]), alkaline phosphatase (ALP: RR: 50 - 375 IU/L), total bilirubin (RR: 3.42 - 22.23 micromoles [umol]/L), albumin grams [g/L], alanine amino transferase (ALT, RR: 5-30 IU/L), prothrombin international normalized ratio (PT INR, RR-0.9 - 1.2), activated partial thromboplastin time (APTT, RR: 24.2 - 32.9 seconds), glucose (RR: 4.107- 6.55018 millimoles [mmol]/L), potassium (3 - 5 mmol/L), and sodium (135 - 143 mmol/L). Baseline values were obtained at Day 1. The number of participants with the indicated clinical chemistry data outside of the reference range (with high and low) any time post-Baseline are presented. Anytime post-Baseline assesments included any scheduled and unscheduled post-Baseline assessment
Time Frame Post-Baseline from Week 1 through Follow-up up to Study Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Part 1 (Dose-Finding Period) Part 2 (Randomized Period) -Placebo Part 2 (Randomized Period) - Eltrombopag Part 2/3 (Eltrombopag Open-Label Period)
Hide Arm/Group Description:
Participants (par) aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 24 weeks. The starting dose for Cohort 1 was 25 mg, and par of East Asian ancestry received 12.5mg QD. For cohort 2 starting dose was based on the body weight. Par with a body weight of <27 kg received 12.5 mg QD, par with a body weight of >=27 kg received 25 mg QD; par of east Asian ancestry with a body weight <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 0.7 mg/kg QD and 0.5 mg/kg/day for par of East Asian ancestry and the dose calculations were based on the body weight. The maximum dose allowed for all Cohorts was 75mg daily. For all par, individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag matching placebo for 7 weeks.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 7 weeks. The starting dose for Cohort 1 was 37.5 mg QD. For Cohort 2, starting dose was based on the body weight. Par with a body weight of <27 kg received 25 mg QD, and par with a body weight of >=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 1.5 mg/kg QD and 0.8 mg/kg/day for par of East Asian ancestry. The maximum dose allowed was 2mg/kg and could not exceed 75 mg daily. For all par, individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3: 1 to 5 years), completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet or dry powder for oral suspension in Part 2/3. Par who received eltrombopag during the Randomized Period continued on the same dose, unless adjustments were warranted according to the dosing guidelines, for 17 additional weeks (for a total of 24 weeks of treatment). Par who received placebo during the Randomized Period followed the starting doses for each age Cohort specified for Part 2, and received a total of 24 weeks of eltrombopag treatment.
Overall Number of Participants Analyzed 15 21 44 65
Measure Type: Number
Unit of Measure: Participants
AST high, n=15, 21, 44, 65 5 4 7 17
AST low, n=15, 21, 44, 65 1 1 3 7
ALT, high, n= 15, 21, 44, 65 2 3 3 14
ALT, low, n= 15, 21, 44, 65 2 3 4 11
Total Bilirubin, high, n=15, 21, 44, 65 5 2 2 9
Total Bilirubin, low, n=15, 21, 44, 65 6 0 16 31
Direct Bilirubin, high, n=10, 16, 34, 55 0 1 1 3
Direct Bilirubin, low, n=10, 16, 34, 55 1 0 6 8
Albumin, high, n=15, 21, 24, 65 3 3 2 9
Albumin, low, n=15, 21, 24, 65 1 3 5 11
ALP, high, n=15, 21, 24, 65 4 1 6 13
ALP, low, n=15, 21, 24, 65 2 2 4 11
PT INR, high, n=15, 20, 42, 64 2 1 4 12
PT INR, low, n=15, 20, 42, 64 0 0 0 1
PT, high, n=13, 20, 36, 61 5 5 8 24
PT, low, n=13, 20, 36, 61 0 1 0 3
PTT, high, n=15, 21, 41, 63 4 2 1 11
PTT, low, n=15, 21, 41, 63 0 1 1 9
Glucose, high, n=15, 21, 44, 65 5 5 7 27
Glucose, low, n=15, 21, 44, 65 7 6 16 29
Potassium, high, n=15, 21, 44, 65 7 0 3 9
Potassium, low, n=15, 21, 44, 65, 3 4 8 14
Sodium, high, n=15, 21, 44, 65 2 1 2 6
Sodium, low, n=15, 21, 44, 65 2 1 4 9
21.Secondary Outcome
Title Number of Participants With the Indicated Hematology Parameters Falling Outside of the Reference Range at Any Time Post-Baseline During Part 1, Part 2, and Part 2/3
Hide Description Hematology parameters included: erythrocytes (RR: 4.2 - 6.1 teragrams per liter [TI/L]), hemoglobin (RR: 125 - 165 g/L), hematocrit (RR: 0.36 - 0.46), platelets (RR: 170 - 430 gigagrams per liter [GI/L]), mean platelet volume (MPV, RR: 4 - 14 femotoliter [fL]), leukocytes (RR: 3.4 - 11.2 GI/L), total neutrophils (RR: 2.1 - 4.9 GI/L), lymphocytes (RR: 1.4 - 2.9 GI/L), monocytes (RR: 0.2 - 0.9 GI/L), eosinophils (RR: 0.2 - 0.7 GI/L), and basophils (RR: 0.02 - 0.12 GI/L). Baseline values were obtained at Day 1. The number of participants with the indicated hematology parameters data outside of the reference range (with high and low) any time post-baseline are presented. Anytime post-Baseline assesments included any scheduled and unscheduled post-Baseline assessment
Time Frame Post-Baseline from Week 1 through Follow-up up to Study Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Part 1 (Dose-Finding Period) Part 2 (Randomized Period) -Placebo Part 2 (Randomized Period) - Eltrombopag Part 2/ 3 (Eltrombopag Open-Label Period)
Hide Arm/Group Description:
Participants (par) aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 24 weeks. The starting dose for Cohort 1 was 25 mg, and par of East Asian ancestry received 12.5mg QD. For cohort 2 starting dose was based on the body weight. Par with a bodyweight of <27 kg received 12.5 mg QD, par with a body weight of >=27 kg received 25 mg QD; par of east Asian ancestry with a body weight <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 0.7 mg/kg QD and 0.5 mg/kg/day for par of East Asian ancestry and the dose calculations were based on the body weight. The maximum dose allowed for all Cohorts was 75mg daily. For all par, individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag matching placebo for 7 weeks.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 7 weeks. The starting dose for Cohort 1 was 37.5 mg QD. For Cohort 2, starting dose was based on the body weight. Par with a body weight of <27 kg received 25 mg QD, and par with a body weight of >=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 1.5 mg/kg QD and 0.8 mg/kg/day for par of East Asian ancestry. The maximum dose allowed was 2mg/kg and could not exceed 75 mg daily. For all par, individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3: 1 to 5 years), completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet or dry powder for oral suspension in Part 2/3. Par who received eltrombopag during the Randomized Period continued on the same dose, unless adjustments were warranted according to the dosing guidelines, for 17 additional weeks (for a total of 24 weeks of treatment). Par who received placebo during the Randomized Period followed the starting doses for each age Cohort specified for Part 2, and received a total of 24 weeks of eltrombopag treatment.
Overall Number of Participants Analyzed 15 21 44 65
Measure Type: Number
Unit of Measure: Participants
Erythrocytes high, n=15, 21, 44, 65 5 0 7 15
Erythrocytes low, n=15, 21, 44, 65 2 8 13 24
Hemoglobin, high, n= 15, 21, 44, 65 2 2 2 8
Hemoglobin low, n= 15, 21, 44, 65 10 5 15 32
Hematocrit, high, n=15, 21, 44, 65 1 0 0 5
Hematocrit, low, n=15, 21, 44, 65 10 11 22 39
Platelets, high, n=15, 21, 44, 65 9 0 6 14
Platelets, low, n=15, 21, 44, 65 15 21 44 65
Leukocytes, high, n=15, 21, 44, 65 6 5 8 27
Leukocytes, low, n=15, 21, 44, 65 4 5 10 19
Neutrophils, high, n=15, 21, 44, 65 7 5 11 33
Neutrophils, low, n=15, 21, 44, 65 3 4 10 21
Lymphocytes, high, n=15, 21, 44, 65 1 3 5 11
Lymphocytes, low, n=15, 21, 44, 65 5 6 10 25
Monocytes, high, n=15, 21, 44, 65 3 3 7 15
Monocytes, low, n=15, 21, 44, 65 4 7 10 23
Eosinophils, high, n=15, 21, 44, 65 5 3 11 24
Eosinophils, low, n=15, 21, 44, 65 4 2 5 9
Basophils, high, n=15, 21, 44, 65 6 5 10 20
Basophils, low, n=15, 21, 44, 65 2 0 1 1
Mean Platelet Volume, high, n=12, 17, 40, 59 10 10 23 47
Mean Platelet Volume, low, n=12, 17, 40, 59 4 6 10 16
22.Secondary Outcome
Title Number of Participants With the Indicated Renal Parameters Falling Outside of the Reference Range Any Time Post-Baseline During Part 1, Part 2, and Part 2/3
Hide Description Renal parameters included: creatinine (RR: 44.2 - 88.4 umol/L), creatinine clearance derived (RR: 89.0 - 165.0 milliliter per minute [ ml/min]), protein/creatinine (RR: 0.113- 18.0992 microgram per millimoles [mg/mmol]), and urea (RR: 1.785- 8.925 mmol/L). Baseline values were obtained at Day 1. The number of participants with the indicated renal parameters data outside the reference range (with high and low) any time post-Baseline are presented. Anytime post-Baseline assesments included any scheduled and unscheduled post-baseline assessment
Time Frame Post-Baseline from Week 1 through Follow-up up to Study Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Part 1 (Dose-Finding Period) Part 2 (Randomized Period) -Placebo Part 2 (Randomized Period) - Eltrombopag Part 2/ 3 (Eltrombopag Open-Label Period)
Hide Arm/Group Description:
Participants aged between 1 and 17 years (Cohort 1 age group- 12 to 17 years, Cohort 2- 6 to 11 years and Cohort 3-1 to 5 years) received eltrombopag for 24 weeks. The starting dose for cohort 1 was eltrombopag 25 mg, (East Asian ancestry: 12.5mg, QD). For cohort 2 starting dose was based on the body weight (Weight <27 kg: 25 mg QD, Weight >=27 kg: 50 mg QD; east Asian ancestry subjects Weight <27 kg: 12.5 mg QD, Weight >=27 kg: 25 mg QD). For cohort 1 and 2 maximum dose allowed was 75mg. For cohort 3 starting dose was 0.7 mg/kg, QD and the dose calculations were based on the body weight. For all participants individual dose titration was allowed based upon platelet response.
Participants aged between 1 and 17 years (Cohort 1 age group- 12 to 17 years, Cohort 2- 6 to 11 years and Cohort 3- 1 to 5 years) received eltrombopag matching placebo for 7 weeks.
Participants aged between 1 and 17 years (Cohort 1 age group- 12 to 17 years, Cohort 2- 6 to 11 years and Cohort 3-1 to 5 years) received eltrombopag for 7 weeks. The starting dose for cohort 1 was eltrombopag 25 mg, (East Asian ancestry: 12.5mg, QD). For cohort 2 starting dose was based on the body weight (Weight <27 kg: 25 mg QD, Weight >=27 kg: 50 mg QD; east Asian ancestry subjects Weight <27 kg: 12.5 mg QD, Weight >=27 kg: 25 mg QD). For cohort 1 and 2 maximum dose allowed was 75mg. For cohort 3 starting dose was 0.7 mg/kg, QD and the dose calculations were based on the body weight. For all participants individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3: 1 to 5 years), completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet or dry powder for oral suspension in Part 2/3. Par who received eltrombopag during the Randomized Period continued on the same dose, unless adjustments were warranted according to the dosing guidelines, for 17 additional weeks (for a total of 24 weeks of treatment). Par who received placebo during the Randomized Period followed the starting doses for each age Cohort specified for Part 2, and received a total of 24 weeks of eltrombopag treatment.
Overall Number of Participants Analyzed 15 21 44 65
Measure Type: Number
Unit of Measure: Participants
Creatinine, high, n=15, 21, 44, 65 1 3 6 13
Creatinine, low, n=15, 21, 44, 65 5 4 4 12
Creatinine Clearance Derived, high, n=15, 21,44,65 11 17 28 46
Creatinine Clearance Derived, low, n=15, 21,44,65 0 2 3 4
Protein/Creatinine, high, n=12, 19, 38, 58 1 2 4 18
Protein/Creatinine, low, n=12, 19, 38, 58 1 0 0 0
Urea, high, n=15, 21, 44, 65 1 2 2 5
Urea, low, n=15, 21, 44, 65 5 1 9 11
23.Secondary Outcome
Title Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1
Hide Description Urine microscopy included Red Blood Cell (RBC) casts, white blood cell (WBC) casts, and epithelial renal tubular cell casts. Urine microscopy data was reviewed by the Medical Monitor in order to classify the results as positive or negative. The number of participants with a positive result at any time post Baseline were reported. A positive result indicated if the result was positive for at least one of RBC casts, WBC casts, or epithelial renal tubular cell casts.
Time Frame From Baseline up to Study Week 24 of Part 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population, only those participants enrolled during Part 1 were analyzed.
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Measure Type: Number
Unit of Measure: Participants
Epithelial Renal Cell Casts 0 0 2
RBC Casts 0 0 0
WBC Casts 0 0 0
24.Secondary Outcome
Title Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2
Hide Description Urine microscopy included Red Blood Cell (RBC) casts, white blood cell (WBC) casts, and epithelial renal tubular cell casts. Urine microscopy data was reviewed by the Medical Monitor in order to classify the results as positive or negative. The nmber of participants with positive finding at Baseline and at anytime post-Baseline (Post-BL) were reported. Baseline was defined as the value obtained at the first visit before treatment (Pre-trt). A positive result indicated if the result was positive for at least one of RBC casts, WBC casts, or epithelial renal tubular cell casts.
Time Frame From Baseline and post-Baseline up to Study Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population, only those participants enrolled during Part 2 were analyzed.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 17 4 11
Measure Type: Number
Unit of Measure: Participants
Pre-trt Epithelial Renal Tubular Cell Casts 0 2 0 0 0 0
Pre-trt RBC Casts 0 1 0 0 0 0
Pre-trt WBC Casts 0 0 0 0 0 0
Post-BL Epithelial Renal Tubular Cell Casts 1 3 0 0 1 0
Post-BL RBC Casts 0 0 0 0 0 0
Post-BL WBC Casts 0 0 0 0 0 1
25.Secondary Outcome
Title Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3
Hide Description Urine microscopy included Red Blood Cell (RBC) casts, white blood cell (WBC) casts, and epithelial renal tubular cell casts. Urine microscopy data was reviewed by the Medical Monitor in order to classify the results as positive or negative. The number of participants with positive finding at Baseline and at anytime post-Baseline (Post-BL) were reported. Baseline was defined as the value obtained at the first visit before treatment (Pre-trt). A positive result indicated if the result was positive for at least one of RBC casts, WBC casts, or epithelial renal tubular cell casts. Participants randomized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.
Time Frame From Baseline and post-Baseline up to Study Week 31 of Part 2/3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population, only those participants enrolled during Part 2/3 were analyzed.
Arm/Group Title Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open- Label Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 26 15
Measure Type: Number
Unit of Measure: Participants
Pre-trt Epithelial Renal Tubular Cell Casts 3 0 1
Pre-trt RBC Casts 1 0 0
Pre-trt WBC Casts 0 0 0
Post-BL Epithelial Renal Tubular Cell Casts 3 2 1
Post-BL RBC Casts 0 0 1
Post-BL WBC Casts 1 0 1
26.Secondary Outcome
Title Number of Participants With the Indicated Vital Signs Falling Outside of the Reference Range During Part 1, Part 2, and Part 2/3
Hide Description Vital sign assessments included systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements that were measured before any blood draw at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, at each Follow-up week (Week 1-4) and the maximum post- Baseline (BL) visit. BL is defined as the value obtained on Day 1of treatment. The maximum post-BL visit (MPB) included any scheduled and unscheduled post-BL assessment. Reference ranges (RR) for SBP (mmHg) (Lower limit of normal, normal, Upper limit of normal) for Cohort 1: <85, 85-115, >115; for Cohort 2: <85, 85-120,>120; and Cohort 3: <95, 95-135, >135. RR for DBP (mmHg) for Cohort 1: <45, 45-70,>70; for Cohort 2: <50, 50-75, >75; and Cohort 3: <55, 55-85, >85.
Time Frame From Baseline through Study Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Part 1 Eltrombopag Dose-Finding Period Part 2 Randomized Period - Placebo Part 2 Randomized Period - Eltrombopag Part 2/ 3 (Eltrombopag Open-Label Period)
Hide Arm/Group Description:
Participants (par) aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 24 weeks. The starting dose for Cohort 1 was 25 mg, and par of East Asian ancestry received 12.5mg QD. For cohort 2 starting dose was based on the body weight. Par with a bodyweight of <27 kg received 12.5 mg QD, par with a body weight of >=27 kg received 25 mg QD; par of east Asian ancestry with a body weight <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 0.7 mg/kg QD and 0.5 mg/kg/day for par of East Asian ancestry and the dose calculations were based on the body weight. The maximum dose allowed for all Cohorts was 75mg daily. For all par, individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag matching placebo for 7 weeks.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 7 weeks. The starting dose for Cohort 1 was 37.5 mg QD. For Cohort 2, starting dose was based on the body weight. Par with a body weight of <27 kg received 25 mg QD, and par with a body weight of >=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 1.5 mg/kg QD and 0.8 mg/kg/day for par of East Asian ancestry. The maximum dose allowed was 2mg/kg and could not exceed 75 mg daily. For all par, individual dose titration was allowed based upon platelet response.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3: 1 to 5 years), completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet or dry powder for oral suspension in Part 2/3. Par who received eltrombopag during the Randomized Period continued on the same dose, unless adjustments were warranted according to the dosing guidelines, for 17 additional weeks (for a total of 24 weeks of treatment). Par who received placebo during the Randomized Period followed the starting doses for each age Cohort specified for Part 2, and received a total of 24 weeks of eltrombopag treatment.
Overall Number of Participants Analyzed 15 21 44 65
Measure Type: Number
Unit of Measure: Participants
Screening, DBP, high, n=15 ,20 ,41 ,40 1 4 3 3
Screening, DBP, low, n=15, 20, 41, 40 0 2 6 5
Day 1, DBP, high, n=14, 18, 38, 59 2 4 3 7
Day 1, DBP, low, n=14, 18, 38, 59 1 1 3 4
Week 1, DBP, high, n=14, 19, 42, 63 1 3 4 5
Week 1, DBP, low, n=14, 19, 42, 63 1 1 4 5
Week 2, DBP, high, n=15, 20, 42, 61 3 2 2 3
Week 2, DBP, low, n=15, 20, 42, 61 2 3 4 5
Week 3, DBP, high,n=15, 21, 41, 60 1 3 3 6
Week 3, DBP, low,n=15, 21, 41, 60 2 3 5 5
Week 4, DBP,high, n=15, 21, 42, 62 0 3 3 6
Week 4, DBP,low, n=15, 21, 42, 62 4 4 3 5
Week 5, DBP, high, n=15, 19, 40, 59 1 2 4 8
Week 5, DBP, low, n=15, 19, 40, 59 1 1 5 5
Week 6, DBP, high, n=14, 21, 42, 58 1 2 3 5
Week 6, DBP, low, n=14, 21, 42, 58 0 0 3 4
Week 7, DBP, high, n=15, 21, 42, 58 1 4 6 7
Week 7, DBP, low, n=15, 21, 42, 58 0 1 2 4
Week 8, DBP,high,n=15, 0, 0, 49 0 NA [1]  NA [1]  4
Week 8, DBP,low,n=15, 0, 0, 49 1 NA [1]  NA [1]  6
Week 9, DBP, high, n=15, 0, 0, 45 2 NA [1]  NA [1]  4
Week 9, DBP, low, n=15, 0, 0, 45 1 NA [1]  NA [1]  6
Week 10, DBP, high, n=15, 0, 0, 40 0 NA [1]  NA [1]  6
Week 10, DBP, low, n=15, 0, 0, 40 0 NA [1]  NA [1]  3
Week 11, DBP, high, n=13, 0, 0, 41 0 NA [1]  NA [1]  4
Week 11, DBP, low, n=13, 0, 0, 41 2 NA [1]  NA [1]  3
Week 12, DBP, high, n=13, 0, 0, 42 0 NA [1]  NA [1]  5
Week 12, DBP, low, n=13, 0, 0, 42 3 NA [1]  NA [1]  3
Week 13, DBP, high, n=12, 0, 0, 32 0 NA [1]  NA [1]  0
Week 13, DBP, low, n=12, 0, 0, 32 0 NA [1]  NA [1]  5
Week 14, DBP, high, n=9, 0, 0, 32 0 NA [1]  NA [1]  3
Week 14, DBP, low, n=9, 0, 0, 32 1 NA [1]  NA [1]  3
Week 15, DBP, high, n=11, 0, 0, 31 1 NA [1]  NA [1]  3
Week 15, DBP, low, n=11, 0, 0, 31 2 NA [1]  NA [1]  0
Week 16, DBP,high,n=12, 0, 0, 39 0 NA [1]  NA [1]  2
Week 16, DBP,low,n=12, 0, 0, 39 0 NA [1]  NA [1]  3
Week 17, DBP,high,n=5, 0, 0, 29 0 NA [1]  NA [1]  2
Week 17, DBP,low,n=5, 0, 0, 29 1 NA [1]  NA [1]  1
Week 18, DBP,high,n=9, 0, 0, 32 0 NA [1]  NA [1]  3
Week 18, DBP,low,n=9, 0, 0, 32 1 NA [1]  NA [1]  1
Week 19, DBP,high,n=5, 0, 0, 34 0 NA [1]  NA [1]  1
Week 19, DBP,low,n=5, 0, 0, 34 0 NA [1]  NA [1]  2
Week 20, DBP,high,n=13, 0, 0, 33 0 NA [1]  NA [1]  0
Week 20, DBP,low,n=13, 0, 0, 33 0 NA [1]  NA [1]  1
Week 21, DBP,high,n=10, 0, 0, 17 1 NA [1]  NA [1]  1
Week 21, DBP,low,n=10, 0, 0, 17 1 NA [1]  NA [1]  1
Week 22, DBP,high,n=11, 0, 0, 23 1 NA [1]  NA [1]  1
Week 22, DBP,low,n=11, 0, 0, 23 1 NA [1]  NA [1]  0
Week 23, DBP,high,n=11, 0, 0, 21 0 NA [1]  NA [1]  1
Week 23, DBP,low,n=11, 0, 0, 21 2 NA [1]  NA [1]  2
Week 24 DBP,high,n=15, 0, 0, 58 0 NA [1]  NA [1]  5
Week 24, DBP,low,n=15, 0, 0, 58 3 NA [1]  NA [1]  3
FU Week 1, DBP,high,n=5, 0, 0, 13 1 NA [1]  NA [1]  2
FU Week 1, DBP,low,n=5, 0, 0, 13 1 NA [1]  NA [1]  1
FU Week 2, DBP,high,n=5, 0, 0, 21 0 NA [1]  NA [1]  2
FU Week 2, DBP,low,n=5, 0, 0, 21 0 NA [1]  NA [1]  1
FU Week 3, DBP,high,n=5, 0, 0, 14 0 NA [1]  NA [1]  2
FU Week 3, DBP,low,n=5, 0, 0, 14 0 NA [1]  NA [1]  0
FU Week 4, DBP,high,n=3, 0, 0, 31 0 NA [1]  NA [1]  7
FU Week 4, DBP,low,n=3, 0, 0, 31 1 NA [1]  NA [1]  5
Screening, SBP, high, n=15, 20, 41, 40 4 4 10 10
Screening, SBP, low, n=15, 20, 41, 40 3 0 3 2
Day 1, SBP,high,n=14, 18, 38, 59 4 5 9 14
Day 1, SBP,low,n=14, 18, 38, 59 0 1 4 4
Week 1, SBP,high,n=14, 19, 42, 63 3 6 14 18
Week 1, SBP,low,n=14, 19, 42, 63 2 0 4 8
Week 2, SBP,high,n=15, 20, 43, 62 4 7 7 15
Week 2, SBP,low,n=15, 20, 43, 62 1 2 5 6
Week 3, SBP,high,n=15, 21, 41, 60 3 4 12 17
Week 3, SBP,low,n=15, 21, 41, 60 1 2 2 3
Week 4, SBP,high,n=15, 21, 42, 62 4 6 10 16
Week 4, SBP,low,n=15, 21, 42, 62 4 1 3 2
Week 5, SBP,high,n=15, 19, 40, 59 5 5 13 17
Week 5, SBP, low, n=15, 19, 40, 59 2 1 3 3
Week 6, SBP,high,n=14, 21, 42, 58 4 8 11 16
Week 6, SBP,low,n=14, 21, 42, 58 2 1 3 5
Week 7, SBP,high,n=15, 21, 42, 58 5 5 9 13
Week 7, SBP,low,n=15, 21, 42, 58 1 0 2 5
Week 8, SBP,high,n=15, 0, 0, 49 3 NA [1]  NA [1]  16
Week 8, SBP,low,n=15, 0, 0, 49 4 NA [1]  NA [1]  4
Week 9, SBP,high,n=15, 0, 0, 45 4 NA [1]  NA [1]  15
Week 9, SBP,low,n=15, 0, 0, 45 3 NA [1]  NA [1]  2
Week 10, SBP,high,n=15, 0, 0, 40 2 NA [1]  NA [1]  10
Week 10, SBP,low,n=15, 0, 0, 40 2 NA [1]  NA [1]  3
Week 11, SBP,high,n=13, 0, 0, 41 4 NA [1]  NA [1]  9
Week 11, SBP,low,n=13, 0, 0, 41 2 NA [1]  NA [1]  2
Week 12, SBP,high,n=13, 0, 0, 42 3 NA [1]  NA [1]  10
Week 12, SBP,low,n=13, 0, 0, 42 3 NA [1]  NA [1]  3
Week 13, SBP,high,n=12, 0, 0, 32 3 NA [1]  NA [1]  8
Week 13, SBP,low,n=12, 0, 0, 32 2 NA [1]  NA [1]  3
Week 14, SBP,high,n=9, 0, 0, 32 4 NA [1]  NA [1]  10
Week 14, SBP,low,n=9, 0, 0, 32 0 NA [1]  NA [1]  3
Week 15, SBP,high,n=11, 0, 0, 31 3 NA [1]  NA [1]  9
Week 15, SBP,low,n=11, 0, 0, 31 2 NA [1]  NA [1]  1
Week 16 SBP,high,n=12, 0, 0, 39 5 NA [1]  NA [1]  14
Week 16, SBP,low,n=12, 0, 0, 39 1 NA [1]  NA [1]  1
Week 17, SBP,high,n=5, 0, 0, 29 1 NA [1]  NA [1]  9
Week 17, SBP,low,n=5, 0, 0, 29 1 NA [1]  NA [1]  0
Week 18, SBP,high,n=9, 0, 0, 32 2 NA [1]  NA [1]  10
Week 18, SBP,low,n=9, 0, 0, 32 0 NA [1]  NA [1]  1
Week 19, SBP,high,n=5, 0, 0, 34 2 NA [1]  NA [1]  9
Week 19, SBP,low,n=5, 0, 0, 34 0 NA [1]  NA [1]  2
Week 20, SBP,high,n=13, 0, 0, 33 6 NA [1]  NA [1]  10
Week 20, SBP,low,n=13, 0, 0, 33 2 NA [1]  NA [1]  1
Week 21, SBP,high,n=10, 0, 0, 17 2 NA [1]  NA [1]  0
Week 21, SBP,low,n=10, 0, 0, 17 3 NA [1]  NA [1]  0
Week 22, SBP,high,n=11, 0, 0, 23 2 NA [1]  NA [1]  8
Week 22, SBP,low,n=11, 0, 0, 23 3 NA [1]  NA [1]  0
Week 23, SBP,high,n=11, 0, 0, 21 2 NA [1]  NA [1]  6
Week 23, SBP,low,n=11, 0, 0, 21 2 NA [1]  NA [1]  1
Week 24, SBP,high,n=15, 0, 0, 58 4 NA [1]  NA [1]  19
Week 24, SBP, low, n=15, 0, 0, 58 2 NA [1]  NA [1]  2
FU Week 1, SBP, high,n=5, 0, 0, 13 0 NA [1]  NA [1]  4
FU Week 1, SBP, low,n=5, 0, 0, 13 2 NA [1]  NA [1]  0
FU Week 2, SBP, high,n=5, 0, 0, 21 2 NA [1]  NA [1]  3
FU Week 2, SBP, low,n=5, 0, 0, 21 0 NA [1]  NA [1]  3
FU Week 3, SBP, high,n=5, 0, 0, 14 1 NA [1]  NA [1]  4
FU Week 3, SBP, low,n=5, 0, 0, 14 0 NA [1]  NA [1]  0
FU Week 4, SBP, high,n=3, 0, 0, 31 1 NA [1]  NA [1]  10
FU Week 4, SBP,low,n=3, 0, 0, 31 1 NA [1]  NA [1]  3
[1]
Part 2 ended at Week 7 so no participants were analyzed for this parameter at this time point.
27.Secondary Outcome
Title Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1
Hide Description Respiratory rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline value included any scheduled and unscheduled post-Baseline assessment.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population .
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Mean (Standard Deviation)
Unit of Measure: Breaths per min
BL, n=4, 5, 4 20.0  (0.00) 21.4  (4.10) 25.5  (4.43)
Week 1, n=4,5,4 21.5  (4.43) 22.0  (6.00) 26.5  (6.40)
Week 2, n=5,5,4 20.6  (3.44) 19.4  (4.98) 24.0  (5.42)
Week 3, n=5,5,5 22.0  (5.66) 17.0  (5.10) 23.6  (6.07)
Week 4, n=5,5,5 18.8  (1.79) 17.2  (4.82) 25.4  (5.98)
Week 5, n=5,5,4 20.4  (2.19) 20.2  (6.87) 24.3  (5.56)
Week 6, n=5,5,4 18.4  (2.61) 20.2  (5.02) 24.5  (2.52)
Week 7, n=5,5,5 19.2  (1.10) 23.4  (9.15) 24.4  (6.69)
Week 8, n=5,5,5 19.8  (3.03) 20.4  (3.05) 23.8  (4.82)
Week 9, n=5,4,5 19.2  (2.28) 22.5  (3.79) 22.0  (2.00)
Week 10, n=5,5,5 19.6  (2.61) 18.0  (4.00) 22.4  (1.67)
Week 11, n=5,3,4 19.6  (1.67) 20.3  (3.21) 25.0  (5.03)
Week 12, n=4,3,4 19.5  (1.00) 20.0  (0.00) 27.6  (11.52)
Week 13, n=4,4,4 19.5  (1.00) 21.0  (2.16) 23.0  (3.46)
Week 14, n=3,3,3 18.7  (1.15) 22.7  (1.15) 27.3  (7.57)
Week 15, n=3,3,3 18.0  (2.00) 21.3  (1.15) 24.0  (2.00)
Week 16, n=5,3,4 18.8  (3.35) 20.0  (4.00) 30.8  (16.88)
Week 17, n=2,0,3 18.0  (0.00) NA [1]   (NA) 24.0  (4.00)
Week 18, n=3,3,4 19.3  (1.15) 21.3  (3.06) 29.0  (13.22)
Week 19, n=3,0,2 19.3  (1.15) NA [1]   (NA) 28.0  (11.31)
Week 20, n=5,4,4 19.6  (1.67) 21.5  (3.00) 23.5  (3.42)
Week 21, n=3,2,5 19.3  (1.15) 19.00  (1.41) 23.6  (3.51)
Week 22, n=3,4,3 19.3  (2.31) 21.0  (2.00) 27.3  (7.57)
Week 23, n=4,2,4 20.0  (1.63) 20.0  (0.00) 21.5  (1.91)
Week 24, n=5,5,4 19.6  (0.89) 23.0  (3.16) 24.8  (7.09)
FU Week 1, n=1,1,3 20.0 [2]   (NA) 20.0 [2]   (NA) 22.0  (2.00)
FU Week 2, n=3,2,0 19.3  (1.15) 26.5  (9.19) NA [1]   (NA)
FU Week 3, n=2,1,2 21.0  (4.24) 28.0 [2]   (NA) 24.5  (4.95)
FU Week 4, n=1,0,1 18.0 [2]   (NA) NA [1]   (NA) 24.0 [2]   (NA)
MPB, n=5, 5, 5 24.4  (4.56) 29.8  (6.02) 32.2  (13.90)
[1]
No participants were analyzed for this parameter at this time point.
[2]
There were too few participants available to collect data at this time point to calculate a standard deviation.
28.Secondary Outcome
Title Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2
Hide Description Respiratory rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline value included any scheduled and unscheduled post-Baseline assessment.
Time Frame From Week 1 to Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety Population
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 17 4 11
Mean (Standard Deviation)
Unit of Measure: Breaths per min
BL, n= 5, 14, 9, 12, 3, 10 19.6  (1.67) 18.4  (2.38) 19.4  (3.13) 21.5  (10.03) 18.7  (1.15) 21.4  (2.12)
Week 1, n=7, 16 ,9, 17, 2, 10 19.0  (1.00) 18.8  (1.76) 19.9  (2.26) 20.7  (4.48) 19.0  (1.41) 28.2  (9.54)
Week 2, n=6, 15, 9, 16, 4, 10 19.3  (2.73) 18.9  (2.70) 19.8  (2.33) 23.0  (8.01) 21.5  (5.00) 27.1  (11.70)
Week 3, n=8, 16, 9, 16, 4, 9 18.8  (1.83) 18.9  (1.93) 20.1  (2.76) 22.3  (4.78) 21.0  (2.58) 25.8  (7.17)
Week 4, n=7, 16, 8, 14, 4, 10 19.4  (2.51) 18.6  (2.80) 19.8  (2.49) 21.4  (4.29) 21.5  (1.00) 25.4  (7.18)
Week 5, n=8, 16, 8, 15, 3, 8 19.3  (1.04) 18.5  (2.10) 20.5  (2.98) 19.7  (2.74) 20.0  (2.00) 29.0  (14.77)
Week 6, n=8, 16, 9, 15, 4, 9 20.3  (2.25) 19.4  (2.16) 20.6  (2.19) 20.6  (4.12) 21.0  (1.15) 24.4  (6.69)
Week 7, n=7, 16, 9, 17, 4, 8 20.9  (2.27) 18.4  (1.50) 20.9  (3.33) 20.7  (7.87) 18.5  (1.91) 23.5  (6.12)
MPB, n=8, 16, 9, 17, 4, 11 21.5  (2.33) 21.3  (21.8) 22.7  (2.45) 26.6  (7.87) 23.5  (3.42) 30.0  (13.39)
29.Secondary Outcome
Title Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3
Hide Description Respiratory rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline visit included any scheduled and unscheduled post-Baseline assessment. Participants randomized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.
Time Frame From Week 1 to Follow-up Week 4 of Part 2/3 up to Study Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Part 2/3 (Eltrombopag Period) Cohort 1 Part 2/3 (Eltrombopag Period) Cohort 2 Part 2/3 (Eltrombopag Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 26 15
Mean (Standard Deviation)
Unit of Measure: Breaths per minute
Screening, n=16, 14, 10 18.5  (1.75) 21.2  (6.57) 21.5  (2.56)
Day 1 , n=21, 21, 15 19.2  (2.57) 2.12  (7.74) 21.7  (4.76)
Week 1, n=24, 25, 14 19.1  (1.74) 20.4  (3.93) 25.1  (7.63)
Week 2, n=22, 24, 13 19.4  (2.56) 21.8  (6.85) 25.2  (10.83)
Week 3, n=24, 23, 12 18.8  (1.73) 21.2  (4.40) 24.0  (6.09)
Week 4, n=23, 23, 13 19.0  (2.59) 20.9  (3.82) 24.3  (6.37)
Week 5, n=23, 23, 11 18.9  (2.13) 19.8  (3.19) 26.9  (12.91)
Week 6, n=23, 22, 11 19.3  (2.30) 20.6  (4.11) 23.3  (4.92)
Week 7, n=22, 25, 11 18.8  (1.99) 20.1  (4.46) 22.4  (4.60)
Week 8, n=19, 19, 10 19.2  (2.32) 23.4  (6.23) 22.0  (1.79)
Week 9, n=17, 16, 12 19.5  (2.96) 22.0  (3.95) 22.5  (4.48)
Week 10, n=16, 13, 11 18.7  (2.27) 22.8  (3.83) 23.3  (6.83)
Week 11, n=15, 13, 12 18.9  (1.28) 22.8  (3.11) 22.2  (5.29)
Week 12, n=17, 16, 9 18.6  (1.90) 22.2  (3.76) 23.6  (4.98)
Week 13, n=11, 13, 8 19.3  (1.56) 23.4  (7.68) 21.0  (2.62)
Week 14, n=13, 11, 7 18.7  (2.98) 19.9  (5.49) 23.4  (4.86)
Week 15, n=12, 13, 5 18.7  (1.76) 21.1  (2.53) 24.4  (8.76)
Week 16, n=16, 14, 8 18.6  (1.26) 22.9  (7.97) 24.3  (6.88)
Week 17, n=13, 10, 5 19.0  (2.08) 22.4  (6.45) 25.2  (9.65)
Week 18, n=16, 12, 4 19.1  (3.79) 22.0  (4.53) 29.0  (10.52)
Week 19, n=14, 13, 6 18.1  (1.49) 24.5  (19.33) 24.0  (6.45)
Week 20, n=13, 13, 7 17.4  (1.94) 20.9  (3.52) 33.00  (16.77)
Week 21, n=4, 10, 3 18.8  (3.40) 20.2  (3.55) 28.0  (10.58)
Week 22, n=11, 7, 5 19.7  (2.94) 19.1  (2.79) 26.0  (4.90)
Week 23, n=8, 7, 6 20.4  (2.72) 21.1  (3.24) 23.7  (5.13)
Week 24, n=22, 23, 11 19.1  (2.03) 20.2  (3.11) 23.8  (5.47)
FU Week 1, n=6, 6, 3 18.8  (1.60) 20.0  (3.41) 26.0  (10.39)
FU Week 2, n=6, 5, 7 18.7  (1.63) 20.8  (4.15) 22.2  (4.02)
FU Week 3, n=6, 4, 4 19.0  (1.67) 23.0  (4.16) 24.8  (5.50)
FU Week 4, n=10, 12, 7 19.4  (0.97) 20.8  (1.86) 21.0  (3.74)
MPB, n=24, 26, 15 23.0  (2.78) 27.7  (13.00) 27.7  (11.54)
30.Secondary Outcome
Title Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1
Hide Description Pulse rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline (MPB) visit included any scheduled and unscheduled post-Baseline assessment..
Time Frame From Week 1 to Follow-up Week 4 of Part 1, up to Study Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Safety Population
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Screening, n=5, 5, 5 85.2  (15.71) 88.4  (8.50) 102.0  (7.97)
Day 1, n=4, 5, 5, 84.3  (11.32) 88.2  (12.89) 102.4  (13.22)
Week 1, n= 4, 5, 5 85.3  (4.79) 90.8  (11.19) 103.8  (8.47)
Week 2, n=5, 5, 5 80.4  (12.97) 84.4  (16.77) 96.8  (10.66)
Week 3, n=5, 5, 5 92.8  (31.16) 91.4  (11.04) 106.2  (11.10)
Week 4, n=5, 5, 5 86.4  (10.92) 84.0  (7.62) 98.6  (14.29)
Week 5, n=5, 5, 5 84.6  (9.48) 88.4  (9.58) 107.8  (9.58)
Week 6, n=5, 5, 4 76.4  (10.50) 89.8  (13.79) 103.0  (8.29)
Week 7, n=5, 5, 5 82.0  (9.46) 96.2  (17.84) 103.2  (8.93)
Week 8, n=5, 5, 5 83.0  (5.20) 89.4  (15.04) 111.8  (10.62)
Week 9, n=5, 5, 5 80.4  (13.35) 79.2  (11.34) 101.6  (5.59)
Week 10, n=5, 5, 5 80.6  (14.93) 84.4  (10.31) 105.4  (9.29)
Week 11, n=5, 3, 5 86.6  (11.04) 97.7  (16.50) 106.6  (11.19)
Week 12, n=4, 4, 5 80.5  (12.07) 92.0  (12.83) 101.4  (16.62)
Week 13, n=4, 4, 4 90.8  (15.52) 86.5  (7.05) 103.8  (3.50)
Week 14, n=3, 3, 3 81.0  (9.85) 87.0  (8.66) 101.0  (11.00)
Week 15, n=3, 4, 4 77.3  (6.66) 86.8  (11.87) 102.5  (3.87)
Week 16, n=5, 3, 4 86.4  (18.60) 103.0  (5.57) 93.0  (18.96)
Week 17, n=2, 0, 3 67.5  (20.51) NA [1]   (NA) 97.7  (12.01)
Week 18, n=3, 3, 4 88.0  (10.44) 86.7  (17.01) 102.8  (16.88)
Week 19, n=3, 0, 2 88.0  (20.81) NA [1]   (NA) 94.0  (8.49)
Week 20, n=5, 4, 4 79.8  (13.03) 96.8  (12.58) 111.8  (14.97)
Week 21, n=3, 2, 5 79.0  (6.93) 75.5  (3.54) 101.0  (18.63)
Week 22, n=3, 4, 4 70.3  (14.36) 86.5  (9.04) 100.0  (18.63)
Week 23, n=4, 2, 5 71.5  (13.03) 82.5  (3.54) 100.0  (13.14)
Week 24, n=5, 5, 5 79.6  (7.86) 85.8  (6.91) 96.0  (4.74)
FU Week 1, n=1, 1, 3 81.0 [2]   (NA) 125.0 [2]   (NA) 107.7  (10.79)
FU Week 2, n=3, 2, 0 77.7  (8.74) 84.5  (28.99) NA [1]   (NA)
FU Week 3, n=2, 1, 2 87.0  (2.83) 78.0 [2]   (NA) 98.0  (8.49)
FU Week 4, n=1, 0, 2 89.0 [2]   (NA) NA [1]   (NA) 99.0  (26.87)
MBP, n=5, 5, 5 108.8  (24.01) 109.8  (14.17) 119.6  (5.73)
[1]
There were no participants analyzed at this time point, therefore there is no calculated standard deviation.
[2]
There were too few participants available to collect data at this time point to calculate a standard deviation.
31.Secondary Outcome
Title Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2
Hide Description Pulse rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline visit included any scheduled and unscheduled post-Baseline assessment.
Time Frame From Week 1 to Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was 37.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, unless otherwise approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 17 4 11
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Screening, n=8, 16, 9, 15 80.1  (10.11) 82.8  (17.28) 86.9  (16.10) 94.3  (17.53) 91.5  (6.56) 101.5  (23.48)
Day 1, n=6, 14, 9, 13 77.2  (12.32) 81.3  (8.70) 93.0  (14.04) 88.8  (12.84) 98.7  (5.69) 99.6  (15.84)
Week 1, n=8, 16, 9, 17 76.4  (8.50) 80.1  (12.04) 89.9  (18.48) 98.4  (19.76) 98.5  (13.44) 96.4  (17.08)
Week 2, n=7, 15, 9, 17 79.4  (8.75) 81.7  (9.79) 89.0  (12.44) 91.8  (16.96) 95.3  (7.09) 102.5  (11.81)
Week 3, n=8, 16, 9, 16 81.5  (12.21) 84.0  (10.93) 86.6  (13.39) 95.8  (13.57) 97.0  (14.67) 102.6  (17.44)
Week 4, n=8, 16, 9, 16 76.3  (6.96) 82.4  (10.39) 84.4  (15.91) 91.5  (14.45) 93.5  (17.00) 116.1  (23.26)
Week 5, n=8, 16, 9, 16 79.3  (9.44) 82.5  (13.87) 95.3  (14.96) 92.4  (15.18) 89.0  (15.52) 99.8  (19.51)
Week 6, n=8, 16, 9, 17 77.0  (9.50) 83.2  (11.01) 86.8  (11.62) 90.1  (17.74) 84.8  (13.15) 103.0  (23.14)
Week 7, n=8, 16, 9, 17 74.1  (6.92) 82.8  (11.68) 96.7  (15.39) 91.6  (17.68) 101.5  (16.60) 105.3  (15.18)
MBP, n=8, 16, 9, 17 88.3  (7.72) 97.6  (7.51) 106.1  (11.92) 108.6  (17.08) 106.8  (12.28) 117.5  (21.68)
32.Secondary Outcome
Title Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3
Hide Description Pulse rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline visit included any scheduled and unscheduled post-Baseline assessment. Participants randomized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.
Time Frame From Week 1to Follow-up Week 4 of Part 2/3, up to Study Week 35
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety Population.
Arm/Group Title Part 2/3 (Eltrombopag Period) Cohort 1 Part 2/3 (Eltrombopag Period) Cohort 2 Part 2/3 (Eltrombopag Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 6 and 11 years and completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants with difficulty swallowing a tablet in Part 2 were administered eltrombopag as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag based on body weight up to Week 31 of the study. Participants with a body weight of <=27 kg received 25 mg QD and participants with a body weight of >=27 kg QD received 50 mg QD. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
All participants aged between 1 and 5 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a dry powder for oral suspension in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag up to Week 31 of the study at 1.5 mg/kg QD. Participants of East Asian ancestry received 0.8 mg/kg/day. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 weeks of treatment to complete a total of 24 weeks continuing at the same dosage at the end of Part 2. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 24 26 15
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Screening, n=16, 15, 10 82.8  (17.28) 94.3  (17.53) 104.8  (21.82)
Day 1 , n=22, 22, 15 78.7  (8.67) 92.0  (14.14) 100.8  (15.71)
Week 1, n=24, 26, 14 79.9  (10.82) 94.8  (17.54) 97.8  (15.67)
Week 2, n=23, 26, 13 79.9  (10.02) 92.5  (16.91) 99.8  (12.64)
Week 3, n=24, 24, 12 83.3  (10.63) 95.4  (12.31) 99.4  (16.56)
Week 4, n=24, 25, 13 81.9  (9.81) 91.7  (13.42) 110.6  (22.55)
Week 5, n=24, 24, 11 80.8  (13.00) 91.7  (14.72) 97.4  (17.92)
Week 6, n=23, 24, 11 82.2  (10.45) 91.6  (16.82) 102.8  (20.31)
Week 7, n=22, 25, 11 82.1  (11.47) 91.1  (16.61) 101.5  (16.91)
Week 8, n=19, 20, 10 79.9  (11.85) 90.8  (16.68) 94.2  (25.71)
Week 9, n=17, 16, 12 87.4  (15.75) 91.9  (17.79) 100.9  (15.19)
Week 10, n=16, 13, 11 87.9  (11.74) 94.3  (17.82) 97.8  (18.77)
Week 11, n=15, 14, 12 81.5  (10.20) 89.3  (16.28) 99.3  (15.39)
Week 12, n=17, 16, 9 81.1  (11.98) 91.1  (16.39) 105.3  (19.58)
Week 13, n=11, 13, 8 78.1  (8.47) 97.0  (21.79) 99.5  (20.57)
Week 14, n=13, 12, 7 74.5  (11.15) 94.8  (18.07) 95.6  (12.09)
Week 15, n=12, 14, 5 82.5  (9.41) 94.4  (18.94) 98.0  (8.72)
Week 16, n=17, 14, 8v 81.3  (11.24) 91.4  (15.08) 99.8  (17.16)
Week 17, n=13, 11, 5 79.7  (11.69) 96.1  (20.80) 102.2  (22.61)
Week 18, n=16, 12, 4 81.1  (8.79) 95.8  (23.01) 99.8  (5.56)
Week 19, n=14, 14, 6 82.1  (12.33) 96.5  (20.24) 104.2  (18.88)
Week 20, n=13, 13, 7 79.0  (10.98) 95.9  (17.44) 91.6  (17.18)
Week 21, n=4, 10, 3 82.3  (10.53) 90.3  (10.71) 99.7  (15.28)
Week 22, n=11, 6, 5 83.2  (10.57) 99.7  (5.50) 98.6  (18.20)
Week 23, n=8, 7, 6 80.4  (11.25) 89.0  (22.38) 96.2  (10.68)
Week 24, n=23, 23, 11 81.2  (9.70) 93.5  (12.59) 95.3  (17.75)
FU Week 1, n=6, 6, 3 86.3  (5.85) 94.2  (18.03) 100.0  (20.07)
FU Week 2, n=8, 7, 7 83.0  (8.54) 87.9  (12.77) 110.0  (27.47)
FU Week 3, n=6, 5, 4 83.7  (13.03) 92.4  (11.55) 92.0  (12.19)
FU Week 4, n=11, 13, 7 81.6  (11.89) 92.3  (16.10) 102.3  (18.87)
MPB, n=24, 26, 15 102.2  (9.35) 110.9  (15.03) 121.2  (20.42)
33.Secondary Outcome
Title Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1
Hide Description Urinalysis parameters included: urine protein (UP), urine glucose (UG), urine ketones (UK), urine occult blood (UOB), and pH. The dipstick test gives results in a semi-quantitative manner. UP was categorized as missing (MS), no result (NR), negative (Neg), Trace, 1+, 2+, 3+ and 4+. UG results were categorized as MS, NR, Neg, normal, 5, 15(1+), 30(2+), 60(3+), 110(4+)UK parameters were categorized as as MS, NR, Neg, Trace(5), Small(15), Moderate(40), Large(80), Large(160). UOB parameters were categorized as MS, NR, Neg, 1+, 2+, 3+, Non haemolysed trace, and haemolysed trace. PH results were categorized as MS. NR, normalresult, Neg, and range of pH (from 5-9in increments of 0.5). Data for indicated parameters was reported at Baseline (BL) and Week 24 (W24). The Baseline value was the measurement taken at Day 1.
Time Frame Baseline and Week 24 of Part 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety Population.
Arm/Group Title Part 1 Eltrombopag Dose-Finding Period
Hide Arm/Group Description:
Participants (par) aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 24 weeks. The starting dose for Cohort 1 was 25 mg, and par of East Asian ancestry received 12.5mg QD. For Cohort 2 starting dose was based on the body weight. Par with a bodyweight of <27 kg received 12.5 mg QD, par with a body weight of >=27 kg received 25 mg QD; par of East Asian ancestry with a body weight <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 0.7 mg/kg QD and 0.5 mg/kg/day for par of East Asian ancestry and the dose calculations were based on the body weight. The maximum dose allowed for all Cohorts was 75mg daily. For all par, individual dose titration was allowed based upon platelet response.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: Participants
UP, MS, BL, n=3 1
UP, NR, BL, n=3 0
UP, Neg, BL, n=3 0
UP, Trace, BL, n=3 2
UP, 1+, BL, n=3 0
UP, 2+, BL, n=3 0
UP, 3+, BL, n=3 0
UP, 4+, BL, n=3 0
UG, MS, BL, n=3 0
UG, NR, BL, n=3 0
UG, Neg, BL, n=3 3
UG, normal, BL, n=3 0
UG, 5, BL, n=3 0
UG, 15(1+), BL, n=3 0
UG, 30(2+), BL, n=3 0
UG, 60(3+), BL, n=3 0
UG, 110(4+), BL, n=3 0
UK, MS, BL, n=3 0
UK, NR, BL, n=3 0
UK, Neg, BL, n=3 3
UK, Trace(5), BL, n=3 0
UK, Small(15), BL, n=3 0
UK, Moderate(40), BL, n=3 0
UK, Large(80), BL, n=3 0
UK, Large(160), BL, n=3 0
UOB, MS, BL,n=3 1
UOB, NR, BL,n=3 0
UOB, Neg, BL,n=3 2
UOB, 1+, BL,n=3 0
UOB, 2+, BL,n=3 0
UOB, 3+, BL,n=3 0
UOB, Non haemolysed trace, BL,n=3 0
UOB, haemolysed trace, BL,n=3 0
pH, MS, BL, n=3 0
pH, NR, BL, n=3 0
pH, normal result, BL, n=3 0
pH, Neg, BL, n=3 0
pH, 5, BL, n=3 0
pH, 5.5, BL, n=3 0
pH, 6, BL, n=3 0
pH, 6.5, BL, n=3 1
pH, 7, BL, n=3 0
pH, 7.5,BL, n=3 1
pH, 8, BL, n=3 1
pH, 8.5, BL, n=3 0
pH, 9, BL, n=3 0
UP, MS, W24, n=4 0
UP, NR, W24, n=4 0
UP, Neg, W24, n=4 3
UP, Trace, W24, n=4 1
UP, 1+, W24, n=4 0
UP, 2+, W24, n=4 0
UP, 3+, W24, n=4 0
UP, 4+, W24, n=4 0
UG, MS, W24, n=4 0
UG, NR, W24, n=4 0
UG, Neg, W24, n=4 4
UG, normal, W24, n=4 0
UG, 5, W24, n=4 0
UG, 15(1+), W24, n=4 0
UG, 30(2+), W24, n=4 0
UG, 60(3+), W24, n=4 0
UG, 110(4+), W24, n=4 0
UK, MS, W24, n=4 0
UK, NR, W24, n=4 0
UK, Neg, W24, n=4 3
UK, Trace(5), W24, n=4 1
UK, Small(15), W24, n=4 0
UK, Moderate(40), W24, n=4 0
UK, Large(80), W24, n=4 0
UK, Large(160), W24, n=4 0
UOB, MS, W24, n=4 0
UOB, NR, W24, n=4 0
UOB, Neg, W24, n=4 3
UOB, 1+, W24, n=4 0
UOB, 2+, W24, n=4 0
UOB, 3+, W24, n=4 0
UOB, Non haemolysed trace, W24, n=4 0
UOB, haemolysed trace, W24, n=4 0
pH, MS, W24, n=4 0
pH, NR, W24, n=4 0
pH, normal result, W24, n=4 0
pH, Neg, W24, n=4 0
pH, 5, W24, n=4 0
pH, 5.5, W24, n=4 0
pH, 6, W24, n=4 2
pH, 6.5, W24, n=4 2
pH, 7, W24, n=4 0
pH, 7.5,W24, n=4 0
pH, 8, W24, n=4 0
pH, 8.5, W24, n=4 0
pH, 9, W24, n=4 0
34.Secondary Outcome
Title Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 7 During the Randomized Period,Part 2
Hide Description Urinalysis parameters included: urine protein (UP), urine glucose (UG), urine ketones (UK), urine occult blood (UOB), and pH. The dipstick test gives results in a semi-quantitative manner. UP was categorized as missing (MS), no result (NR), negative (Neg), Trace, 1+, 2+, 3+ and 4+. UG results were categorized as MS, NR, Neg, normal, 5, 15(1+), 30(2+), 60(3+), 110(4+)UK parameters were categorized as as MS, NR, Neg, Trace(5), Small(15), Moderate(40), Large(80), Large(160). UOB parameters were categorized as MS, NR, Neg, 1+, 2+, 3+, Non haemolysed trace, and haemolysed trace. PH results were categorized as MS. NR, normalresult, Neg, and range of pH (from 5-9in increments of 0.5). Data for indicated parameters was reported at Baseline (BL) and Week 7 (W7). The Baseline value was the measurement taken at Day 1.
Time Frame Baseline and Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. 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, so the overall number of participants analyzed reflects everyone in the safety Population
Arm/Group Title Part 2 Randomized Period - Placebo Part 2 Randomized Period - Eltrombopag
Hide Arm/Group Description:
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag matching placebo QD for 7 weeks.
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3:1 to 5 years) received eltrombopag for 7 weeks. The starting dose for Cohort 1 was 37.5 mg QD. For Cohort 2, starting dose was based on the body weight. Par with a body weight of <27 kg received 25 mg QD, and par with a body weight of >=27 kg received 50 mg QD. Par of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD, and with a body weight of >=27 kg received 25 mg QD. For Cohort 3, the starting dose was 1.5 mg/kg QD and 0.8 mg/kg/day for par of East Asian ancestry. The maximum dose allowed was 2mg/kg and could not exceed 75 mg daily. For all par, individual dose titration was allowed based upon platelet response.
Overall Number of Participants Analyzed 21 44
Measure Type: Number
Unit of Measure: Participants
UP, MS, BL, n=10, 9 2 0
UP, NR, BL, n=10, 9 0 1
UP, Neg, BL, n=10, 9 7 8
UP, Trace, BL, n=10, 9 1 0
UP, 1+, BL, n=10, 9 0 0
UP, 2+, BL, n=10, 9 0 0
UP, 3+, BL, n=10, 9 0 0
UP, 4+, BL, n=10, 9 0 0
UG, MS, BL, n=10, 9 2 0
UG, NR, BL, n=10, 9 0 1
UG, Neg, BL, n=10, 9 6 8
UG, normal, BL, n=10, 9 2 0
UG, 5, BL, n=10, 9 0 0
UG, 15(1+), BL, n=10, 9 0 0
UG, 30(2+), BL, n=10, 9 0 0
UG, 60(3+), BL, n=10, 9 0 0
UG, 110(4+), BL, n=10, 9 0 0
UK, MS, BL, n=10, 9 2 0
UK, NR, BL, n=10, 9 0 1
UK, Neg, BL, n=10, 9 8 8
UK, Trace(5), BL, n=10, 9 0 0
UK, Small(15), BL, n=10, 9 0 0
UK, Moderate(40), BL, n=10, 9 0 0
UK, Large(80), BL, n=10, 9 0 0
UK, Large(160), BL, n=10, 9 0 0
UOB, MS, BL, n=9, 9 2 1
UOB, NR, BL, n=9, 9 0 1
UOB, Neg, BL, n=9, 9 6 4
UOB, 1+, BL,n=9, 9 0 1
UOB, 2+, BL,n=9, 9 1 0
UOB, 3+, BL, n=9, 9 0 0
UOB, Non haemolysed trace, BL,n=9, 9 0 0
UOB, haemolysed trace, BL, n=9, 9 0 0
pH, MS, BL, n=10, 9 0 0
pH, NR, BL, n=10, 9 0 1
pH, normal result, BL, n=10, 9 0 0
pH, Neg, BL, n=10, 9 0 0
pH, 5, BL, n=10, 9 1 1
pH, 5.5, BL, n=10, 9 1 1
pH, 6, BL, n=10, 9 3 4
pH, 6.5, BL, n=10, 9 2 1
pH, 7, BL, n=10, 9 1 0
pH, 7.5,BL, n=10, 9 1 1
pH, 8, BL, n=10, 9 1 0
pH, 8.5, BL, n=10, 9 0 0
pH, 9, BL, n=10, 9 0 0
UP, MS, W7, n=2, 3 0 0
UP, NR, W7, n=2, 3 0 0
UP, Neg, W7, n=2, 3 2 3
UP, Trace, W7, n=2, 3 0 0
UP, 1+, W7, n=2, 3 0 0
UP, 2+, W7, n=2, 3 0 0
UP, 3+, W7, n=2, 3 0 0
UP, 4+, W7, n=2, 3 0 0
UG, MS, W7, n=2, 3 0 0
UG, NR, W7, n=2, 3 0 0
UG, Neg, W7, n=2, 3 2 3
UG, normal, W7, n=2, 3 0 0
UG, 5, W7, n=2, 3 0 0
UG, 15(1+), W7, n=2, 3 0 0
UG, 30(2+), W7, n=2, 3 0 0
UG, 60(3+), W7, n=2, 3 0 0
UG, 110(4+), W7, n=2, 3 0 0
UK, MS, W7, n=2, 3 0 0
UK, NR, W7, n=2, 3 0 0
UK, Neg, W7, n=2, 3 2 3
UK, Trace(5), W7, n=2, 3 0 0
UK, Small(15), W7, n=2, 3 0 0
UK, Moderate(40), W7, n=2, 3 0 0
UK, Large(80), W7, n=2, 3 0 0
UK, Large(160), W7, n=2, 3 0 0
UOB, MS, W7, n=2, 3 1 0
UOB, NR, W7, n=2, 3 0 0
UOB, Neg, W7, n=2, 3 1 3
UOB, 1+, W7, n=2, 3 0 0
UOB, 2+, W7, n=2, 3 0 0
UOB, 3+, W7, n=2, 3 0 0
UOB, Non haemolysed trace, W7, n=2, 3 0 0
UOB, haemolysed trace, W7, n=2, 3 0 0
pH, MS, W7, n=2, 3 0 0
pH, NR, W7, n=2, 3 0 0
pH, normal result, W7, n=2, 3 0 0
pH, Neg, W7, n=2, 3 0 0
pH, 5, W7, n=2, 3 1 0
pH, 5.5, W7, n=2, 3 0 0
pH, 6, W7, n=2, 3 0 1
pH, 6.5, W7, n=2, 3 0 1
pH, 7, W7, n=2, 3 1 1
pH, 7.5, W7, n=2, 3 0 0
pH, 8, W7, n=2, 3 0 0
pH, 8.5, W7, n=2, 3 0 0
pH, 9, W7, n=2, 3 0 0
35.Secondary Outcome
Title Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Eltrombopag Open-label Period, Part 2/3
Hide Description Urinalysis parameters included: urine protein (UP), urine glucose (UG), urine ketones (UK), urine occult blood (UOB), and pH. The dipstick test gives results in a semi-quantitative manner. UP was categorized as missing (MS), no result (NR), negative (Neg), Trace, 1+, 2+, 3+ and 4+. UG results were categorized as MS, NR, Neg, normal, 5, 15(1+), 30(2+), 60(3+), 110(4+)UK parameters were categorized as as MS, NR, Neg, Trace(5), Small(15), Moderate(40), Large(80), Large(160). UOB parameters were categorized as MS, NR, Neg, 1+, 2+, 3+, Non haemolysed trace, and haemolysed trace. PH results were categorized as MS. NR, normalresult, Neg, and range of pH (from 5-9in increments of 0.5). Data for indicated parameters was reported at Baseline (BL) and Week 24 (W24). The Baseline value was the measurement taken at Day 1.
Time Frame Baseline and Week 24 of Part 2/3 up to Study Week 31
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the safety population
Arm/Group Title Part 2/ 3 Eltrombopag Open-Label Period
Hide Arm/Group Description:
Par aged between 1 and 17 years (Cohort 1 age group: 12 to 17 years, Cohort 2: 6 to 11 years and Cohort 3: 1 to 5 years), completing Part 2 of the study received an Open -Label treatment of eltrombopag administered as a tablet or dry powder for oral suspension in Part 2/3. Par who received eltrombopag during the Randomized Period continued on the same dose, unless adjustments were warranted according to the dosing guidelines, for 17 additional weeks (for a total of 24 weeks of treatment). Par who received placebo during the Randomized Period followed the starting doses for each age Cohort specified for Part 2, and received a total of 24 weeks of eltrombopag treatment.
Overall Number of Participants Analyzed 44
Measure Type: Number
Unit of Measure: Participants
UP, MS, BL, n=11 0
UP, NR, BL, n=11 1
UP, Neg, BL, n=11 10
UP, Trace, BL, n=11 0
UP, 1+, BL, n=11 0
UP, 2+, BL, n=11 0
UP, 3+, BL, n=11 0
UP, 4+, BL, n=11 0
UG, MS, BL, n=11 0
UG, NR, BL, n=11 1
UG, Neg, BL, n=11 10
UG, normal, BL, n=11 0
UG, 5, BL, n=11 0
UG, 15(1+), BL, n=11 0
UG, 30(2+), BL, n=11 0
UG, 60(3+), BL, n=11 0
UG, 110(4+), BL, n=11 0
UK, MS, BL, n=11 0
UK, NR, BL, n=11 1
UK, Neg, BL, n=11 10
UK, Trace(5), BL, n=11 0
UK, Small(15), BL, n=11 0
UK, Moderate(40), BL, n=11 0
UK, Large(80), BL, n=11 0
UK, Large(160), BL, n=11 0
UOB, MS, BL,n=11 2
UOB, NR, BL,n=11 1
UOB, Neg, BL,n=11 5
UOB, 1+, BL,n=11 1
UOB, 2+, BL,n=11 0
UOB, 3+, BL,n=11 0
UOB, Non haemolysed trace, BL,n=11 0
UOB, haemolysed trace, BL,n=11 0
pH, MS, BL, n=11 0
pH, NR, BL, n=11 1
pH, normal result, BL, n=11 0
pH, Neg, BL, n=11 0
pH, 5, BL, n=11 2
pH, 5.5, BL, n=11 1
pH, 6, BL, n=11 4
pH, 6.5, BL, n=11 1
pH, 7, BL, n=11 1
pH, 7.5,BL, n=11 1
pH, 8, BL, n=11 0
pH, 8.5, BL, n=11 0
pH, 9, BL, n=11 0
UP, MS, W24, n=34 2
UP, NR, W24, n=34 0
UP, Neg, W24, n=34 32
UP, Trace, W24, n=34 0
UP, 1+, W24, n=34 0
UP, 2+, W24, n=34 0
UP, 3+, W24, n=34 0
UP, 4+, W24, n=34 0
UG, MS, W24, n=4 1
UG, NR, W24, n=4 0
UG, Neg, W24, n=33 29
UG, normal, W24, n=33 3
UG, 5, W24, n=33 0
UG, 15(1+), W24, n=33 0
UG, 30(2+), W24, n=33 0
UG, 60(3+), W24, n=33 0
UG, 110(4+), W24, n=33 0
UK, MS, W24, n=33 1
UK, NR, W24, n=33 0
UK, Neg, W24, n=33 32
UK, Trace(5), W24, n=33 0
UK, Small(15), W24, n=33 0
UK, Moderate(40), W24, n=33 0
UK, Large(80), W24, n=33 0
UK, Large(160), W24, n=33 0
UOB, MS, W24, n=33 1
UOB, NR, W24, n=33 0
UOB, Neg, W24, n=33 31
UOB, 1+, W24, n=33 0
UOB, 2+, W24, n=33 0
UOB, 3+, W24, n=33 0
UOB, Non haemolysed trace, W24, n=33 0
UOB, haemolysed trace, W24, n=33 0
pH, MS, W24, n=34 0
pH, NR, W24, n=34 0
pH, normal result, W24, n=34 0
pH, Neg, W24, n=34 0
pH, 5, W24, n=34 0
pH, 5.5, W24, n=34 4
pH, 6, W24, n=34 10
pH, 6.5, W24, n=34 4
pH, 7, W24, n=34 11
pH, 7.5,W24, n=34 3
pH, 8, W24, n=34 2
pH, 8.5, W24, n=34 0
pH, 9, W24, n=34 0
36.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1
Hide 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.
Time Frame From Treatment + 1 day up to Week 24 of Part1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of the investigational product during Part 1 were analyzed.
Arm/Group Title Part 1 (Dose-Finding Period) Cohort 1 Part 1 (Dose-Finding Period) Cohort 2 Part 1 (Dose-Finding Period) Cohort 3
Hide Arm/Group Description:
Participants aged between 12 and 17 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was 25 milligrams (mg), once daily (QD). The participants of East Asian ancestry began at 12.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received a 24-week Open-Label treatment of eltrombopag administered as a tablet. The starting dose of eltrombopag was based on the body weight. Participants with a weight of <27 kilograms (kg) received 12.5 mg QD (approximately 0.5 - 0.7 mg/kg QD) and participants with a weight of >=27 kg received 25 mg QD (approximately 0.5 - 0.8 mg/kg QD). The maximum dose allowed was 2 mg/kg and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 and 5 years received a 24-week Open-Label treatment of eltrombopag administered as a dry powder for oral suspension. The starting dose of eltrombopag was 0.7 mg/kg QD. Participants of East Asian ancestry began at 0.5 mg/kg/day. The maximum dose allowed was 2 mg/kg, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 5 5 5
Measure Type: Number
Unit of Measure: Participants
Any AE 5 5 5
Any SAE 1 1 0
37.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2
Hide 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.
Time Frame From Treatment + 1 day up to Week 7 of Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of the investigational product during Part 2 were analyzed.
Arm/Group Title Part 2 (Randomized Period) Cohort 1-Placebo Part 2 (Randomized Period) Cohort 1- Eltrombopag Part 2 (Randomized Period) Cohort 2-Placebo Part 2 (Randomized Period) Cohort 2-Eltrombopag Part 2 (Randomized Period) Cohort 3-Placebo Part 2 (Randomized Period) Cohort 3- Eltrombopag
Hide Arm/Group Description:
Participants aged between 12 and 17 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 12 and 17 years received eltrombopag administered as a tablet for 7 weeks. The starting dose eltrombopag was 37.5 mg QD. The participants of East Asian ancestry began at 12.5 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 6 and 11 years received eltrombopag matching placebo administered as a tablet QD for 7 weeks.
Participants aged between 6 and 11 years received eltrombopag administered as a tablet for 7 weeks. The starting dose of eltrombopag was based on the body weight, participants with a weight of <27 kg received 25 mg QD and participants with a weight of >=27 kg received 50 mg QD. Participants of East Asian ancestry with a body weight of <27 kg received 12.5 mg QD and participants with a weight of >=27 kg received 25 mg QD. The maximum dose allowed was 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.
Participants aged between 1 to 5 years received eltrombopag administered as a dry powder for oral suspension for 7 weeks. The starting dose of eltrombopag was 1.5 mg/kg QD and the dose calculations were based on the body weight. Participants of East Asian ancestry began at 0.8 mg/kg/day. The maximum dose allowed was 2 mg/kg, as approved by the investigator, and could not exceed 75 mg daily. All participants enrolled in the study underwent individual dose titration based upon platelet response.
Overall Number of Participants Analyzed 8 16 9 17 4 11
Measure Type: Number
Unit of Measure: Participants
Any AE 8 13 9 14 3 9
Any SAE 1 1 1 3 0 0
38.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2/3
Hide 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.
Time Frame From Treatment + 1 day up to Week 31 of Part2/3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who received at least one dose of the investigational product during Part 2/3 were analyzed
Arm/Group Title Part 2/3 (Eltrombopag Open-Label Period) Cohort 1 Part 2/3 (Eltrombopag Open-Label Period) Cohort 2 Part 2/3 (Eltrombopag Open- Label Period) Cohort 3
Hide Arm/Group Description:
All participants aged between 12 and 17 years and completing Part 2 of the study received an Open-Label treatment of eltrombopag administered as a tablet in Part 2/3. Participants who received placebo in Part 2 received 24 weeks of treatment of eltrombopag starting at 37.5 mg QD up to Week 31 of the study. Participants who received 7 weeks of eltrombopag treatment in Part 2 received an additional 17 we