Download PDF

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

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

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

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

TRA115450

ISRCTN number

US NCT number

NCT01520909

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline , +1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, +1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

18 Feb 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

02 Jan 2014

Global end of trial reached?

Yes

Global end of trial date

02 Jan 2014

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of eltrombopag, relative to placebo, in achieving platelet counts of >= 50 Gi/L, when administered to pediatric subjects with previously treated chronic ITP during the first 12 weeks of Part 1, the randomized treatment period.

Protection of trial subjects

Liver stopping criteria – in the instance that liver tests indicate elevated levels, the criteria will advise how to monitor patients as well as study procedure interruption or discontinuation. Dosing Guidelines – guidelines are put into place to ensure, based on individual platelet response, study treatment will maintain platelet counts in a safe hemostatic range, not necessarily in the normal range.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Feb 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 4

Country: Number of subjects enrolled

Czech Republic: 7

Country: Number of subjects enrolled

Germany: 5

Country: Number of subjects enrolled

China: 2

Country: Number of subjects enrolled

Israel: 8

Country: Number of subjects enrolled

Italy: 12

Country: Number of subjects enrolled

Russian Federation: 13

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

United Kingdom: 7

Country: Number of subjects enrolled

Thailand: 25

Country: Number of subjects enrolled

Taiwan: 2

Country: Number of subjects enrolled

United States: 4

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Pediatric participants meeting eligibility criteria were enrolled into 3 cohorts depending upon age. Cohort 1 enrolled participants who were between 12 and 17 years old, Cohort 2 enrolled participants who were between 6 and 11 years old, and Cohort 3 enrolled participants who were between 1 and 5 years old.

Screening details

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

Period 1 title

Part 1 (Randomized Period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Part 1 (Randomized Period)-Placebo

Arm description

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

Arm type

Placebo

Investigational medicinal product name

Placebo to match eltrombopag 12.5mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Tablets were administered once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

Investigational medicinal product name

Placebo to match eltrombopag 25, 50, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Placebo to match eltrombopag 20mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Powder for oral suspension is combined with 9.5mL of water and drawn into a 10cc oral syringe for oral administration once daily at least 2 hours before and 4 hours after any product such as antacids, dairy products, or mineral supplements containing polyvalent cations. Maximum daily dose was not to exceed 75mg.

Part 1 (Randomized Period)-Eltrombopag

Arm description

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

Arm type

Active comparator

Investigational medicinal product name

Eltrombopag 12.5mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 25mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 50mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 20mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Started	29	63
Completed	28	61
Not completed	1	2
Adverse event, non-fatal	1	2

Period 2 title

Part 2 Open-Label Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Part 2 (Open-Label Period) - Eltrombopag

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 12.5mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 25mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 50mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Eltrombopag 20mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2 ^[1]	Part 2 (Open-Label Period) - Eltrombopag
Started	87
Completed	80
Not completed	7
Adverse event, non-fatal	4
Withdrawal by parent/guardian	1
Lack of efficacy	2

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Two participants completed Part 1: Randomized Period but did not endter Part 2: Open-Label Period because the participants withdrew consent.

Baseline characteristics

Top of page

Reporting group title

Part 1 (Randomized Period)-Placebo

Reporting group description

Reporting group title

Part 1 (Randomized Period)-Eltrombopag

Reporting group description

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

End points

Top of page

Reporting group title

Part 1 (Randomized Period)-Placebo

Reporting group description

Reporting group title

Part 1 (Randomized Period)-Eltrombopag

Reporting group description

Reporting group title

Part 2 (Open-Label Period) - Eltrombopag

Reporting group description

Subject analysis set title

Eltrombopag Cohort 1 (12-17 years)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received eltrombopag in Part 1 continued on the same dose in Part 2 unless adjustments were warranted according to the dosing guidelines. Participants who received placebo in Part 1 received Eltrombopag as per age criteria as follows:body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD.

Subject analysis set title

Eltrombopag Cohort 2 (6-11 years)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received eltrombopag in Part 1 continued on the same dose in Part 2 unless adjustments were warranted according to the dosing guidelines. Participants who received placebo in Part 1 received Eltrombopag as per age criteria as follows: body weight <27 kg received eltrombopag 37.5 mg QD, and those with a body weight >=27 kg received eltrombopag 50 mg QD. Participants of East Asian ancestry received a starting dose of eltrombopag 25 mg QD.

Subject analysis set title

Eltrombopag Cohort 3 (1-5 years)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who received eltrombopag in Part 1 continued on the same dose in Part 2 unless adjustments were warranted according to the dosing guidelines. Participants who received placebo in Part 1 received Eltrombopag 1.2 mg/kg QD and; participants of East Asian ancestry received a starting dose of eltrombopag 0.8 mg/kg/day.

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

Top of page

End point title

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

End point description

Participants who achieved a platelet count >=50 Gi/L for at least 6 out of 8 weeks, between Weeks 5 and 12 of Part 1, were reported.

End point type

Primary

End point timeframe

From Week 5 up to Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[1]	63 ^[2]
Units: Participants	1	25

Notes
[1] - Intent-to-Treat (ITT) Population
[2] - Intent-to-Treat (ITT) Population

Statistical Analysis 1

Statistical analysis description

The proportion of participants achieving platelet counts >=50 Gi/L for those participants receiving eltrombopag versus placebo was compared.

Comparison groups

Part 1 (Randomized Period)-Eltrombopag v Part 1 (Randomized Period)-Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

17.96

Confidence interval

level

95%

sides

2-sided

lower limit

2.29

upper limit

140.93

Notes
[3] - Indicated significance at the 5% (two-sided) level of significance

Secondary: Percentage of Responders

Top of page

End point title

Percentage of Responders

End point description

Percentage of participants who responded (defined as platelet count >= 50Gi/L in absence of rescue) at least once up to week 12 of Part 1 (Odds of achieving a platelet count >=50 Gi/L during the first 12 weeks of Part 1)

End point type

Secondary

End point timeframe

From Week 1 up to Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[4]	63 ^[5]
Units: Percentage of Participants
number (not applicable)
Week 1	0	15.9
Week 2	3.4	23.8
Week 3	0	31.7
Week 4	6.9	36.5
Week 5	6.9	47.6
Week 6	6.9	38.1
Week 7	10.3	44.4
Week 8	3.4	44.4
Week 9	3.4	42.9
Week 10	3.4	52.4
Week 11	6.9	49.2
Week 12	3.4	58.7

Notes
[4] - ITT population
[5] - ITT population

Statistical Analysis 1

Comparison groups

Part 1 (Randomized Period)-Placebo v Part 1 (Randomized Period)-Eltrombopag

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[6]

Method

Repeated Measures model for binary data

Parameter type

Odds ratio (OR)

Point estimate

25.33

Confidence interval

level

95%

sides

2-sided

lower limit

8.15

upper limit

78.73

Notes
[6] - Repeated measures model for binary data using Generalized linear mixed model.

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

Top of page

End point title

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

End point description

Participants who achieved a platelet count >=50 Gi/L at any time during the first 12 weeks of Part 1 were reported.

End point type

Secondary

End point timeframe

From Baseline up to Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[7]	63 ^[8]
Units: Participants	6	47

Notes
[7] - ITT population
[8] - ITT population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Participants who achieved a platelet count >=50 Gi/L at any time during the first 6 weeks of Part 1 were reported.

End point type

Secondary

End point timeframe

From Baseline up to Week 6 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[9]	63 ^[10]
Units: Participants	5	39

Notes
[9] - ITT population
[10] - ITT population

No statistical analyses for this end point

Secondary: Weighted mean platelet count

Top of page

End point title

Weighted mean platelet count

End point description

The weighted mean platelet count is defined as "the area under the platelet-time curve divided by the duration of the study (12 weeks)". Weighted mean platelet counts from baseline to week 12 of the randomized period was compared between placebo and eltrombopag using an analysis of covariance model (ANCOVA) adjusting for baseline platelet count and age cohort. For each subject the area between two adjacent visits with platelet counts was calculated. The area was calculated for all pairs of adjacent visits starting at Day 1 of randomized period and then the total sum of all the areas was divided by the total duration of time during the randomized period. For each subject, this method calculates an ‘average’ platelet count and it allows the possibility that subjects may have had different number of assessments during different times relative to baseline.

End point type

Secondary

End point timeframe

Baseline and Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[11]	62 ^[12]
Units: Gi/L
arithmetic mean (standard deviation)
Baseline	14.2 ± 8.01	14 ± 8.09
Week 12	23.7 ± 19.56	63.9 ± 46.68

Notes
[11] - ITT Population. Only those participants with a value at Baseline and post-Baseline were analyzed
[12] - ITT Population. Only those participants with a value at Baseline and post-Baseline were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L was calculated and summarized for the first 12 weeks of Part 1. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If a particpant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.

End point type

Secondary

End point timeframe

From Baseline up to Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[13]	63 ^[14]
Units: Weeks
arithmetic mean (standard deviation)	0.4 ± 1.5	3.3 ± 3.13

Notes
[13] - ITT population
[14] - ITT population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Rescue treatment is defined as either a new immune (idiopathic) thrombocytopenic purpura (ITP) medication, an increase in the dose of a concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy.

End point type

Secondary

End point timeframe

From Baseline up to Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[15]	63 ^[16]
Units: Participants
number (not applicable)	7	12

Notes
[15] - ITT population
[16] - ITT population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross bleeding; Grade 4=debilitating blood loss. The WHO grades were dichotomized into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. Baseline was defined as the Day 1 assessment or the latest possible screening assessment. Only those participants that did not enroll in Part 2 were analyzed during the follow-up visits. Only those participants available at the specified time points were analyzed (represented by n=X,X in the category titles).

End point type

Secondary

End point timeframe

From Baseline through Follow-up of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[17]	63 ^[18]
Units: Participants
number (not applicable)
Baseline, Any bleeding n=29,63	20	45
Baseline, Significant bleeding n=29,63	6	16
Week 1, Any bleeding n=29,63	19	41
Week 1, Significant bleeding n=29,63	3	8
Week 2, Any bleeding n=29,63	19	33
Week 2, Significant bleeding n=29,63	6	6
Week 3, Any bleeding n=28,62	18	32
Week 3, Significant bleeding n=28,62	3	7
Week 4, Any bleeding n=29, 62	20	27
Week 4, Significant bleeding n=29, 62	4	4
Week 5, Any bleeding n=27, 62	18	22
Week 5, Significant bleeding n=27, 62	2	5
Week 6, Any bleeding n=28, 62	17	24
Week 6, Significant bleeding n=28, 62	0	5
Week 7, Any bleeding n=28, 63	14	20
Week 7, Significant bleeding n=28, 63	1	1
Week 8, Any bleeding n=28, 63	17	24
Week 8,Significant bleeding n=28, 63	1	4
Week 9, Any bleeding n=27, 61	18	24
Week 9, Significant bleeding n=27, 61	3	4
Week 10, Any bleeding n=28, 62	17	20
Week 10, Significant bleeding n=28, 62	2	4
Week 11, Any bleeding n=28, 61	16	26
Week 11, Significant bleeding n=28, 61	3	8
Week 12, Any bleeding n=28, 61	16	23
Week 12, Significant bleeding n=28, 61	2	3
Follow-up Week 1, Any bleeding n=0,2	0	1
Follow-up Week 1, Significant bleeding n=0,2	0	0
Follow-up Week 2, Any bleeding n=0,2	0	1
Follow-up Week 2, Significant bleeding n=0,2	0	0
Follow-up Week 3, Any bleeding n=0,3	0	2
Follow-up Week 3, Significant bleeding n=0,3	0	1
Follow-up Week 4, Any bleeding n=0,1	0	1
Follow-up Week 4, Significant bleeding n=0,1	0	1
Any follow-up Week, Any bleeding n=0,3	0	2
Any Follow-up Week, Significant bleeding n=0,3	0	1

Notes
[17] - ITT population
[18] - ITT population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Participants who achieved a platelet count >=50 Gi/L at any time during Part 2 (up to Week 24) were reported.

End point type

Secondary

End point timeframe

From Baseline up to Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[19]
Units: Participants
number (not applicable)	70

Notes
[19] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Platelet response was analyzed after Week 4 for the eltrombopag-only period to allow participants who had been randomized to placebo in the Randomized Period time to escalate to their optimal dose of eltrombopag. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If the participant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.

End point type

Secondary

End point timeframe

From Week 4 up to Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[20]
Units: Weeks
arithmetic mean (standard deviation)	10 ± 7.67

Notes
[20] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The maximum duration for which a participant continuously maintained a platelet count of >=50 Gi/L was calculated and summarized for the 24 weeks of eltrombopag dosing (Part 2). Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If the participant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day.

End point type

Secondary

End point timeframe

From Baseline up to Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[21]
Units: Weeks
arithmetic mean (standard deviation)	8.6 ± 7.84

Notes
[21] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Participants who discontinued or had a sustained reduction of a baseline immune (idiopathic) thrombocytopenic purpura (ITP) medication during the 24 weeks of Part 2 (Open-Label Period) and without requiring subsequent rescue therapy. For participants randomized to placebo in Part 1, Baseline is defined as Week 13 of Part 1. For participants randomized to eltrombopag in Part 1, Baseline is defined as Day 1 of Part 1. A sustained reduction was defined as a reduction for 4 weeks or more. Only those participants who entered into Part 2 (Open-label eltrombopag-only phase) and taking an ITP medication at Baseline were analyzed.

End point type

Secondary

End point timeframe

From Baseline up to Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	15 ^[22]
Units: Participants
number (not applicable)	8

Notes
[22] - ITT population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Rescue treatment was defined as either a new immune (idiopathic) thrombocytopenic purpura (ITP) medication, an increase in the dose of a concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy.

End point type

Secondary

End point timeframe

From Baseline up to Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[23]
Units: Participants
number (not applicable)	11

Notes
[23] - ITT Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The WHO Bleeding Scale is a measure of bleeding severity with the following grades: Grade 0 = no bleeding, Grade 1 = petechiae, Grade 2 = mild blood loss, Grade 3 = gross bleeding and Grade 4 = debilitating blood loss. The WHO Grades were dichotomized into the following categories: no bleeding = Grade 0; any bleeding = Grade 1 to 4; no clinically significant bleeding = Grade 0 to 1; clinically significant bleeding = Grade 2 to 4. Only those participants who entered into Part 2 open-label Eltrombopag only phase were analyzed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

From Baseline of Part 2 through Follow-up

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[24]
Units: Participants
number (not applicable)
Baseline, Any bleeding n=87	55
Baseline, Significant bleeding n=87	17
Week 1, Any bleeding n=86	29
Week 1, Significant bleeding n=86	3
Week 2, Any bleeding n=85	22
Week 2, Significant bleeding n=85	2
Week 3, Any bleeding n=86	20
Week 3, Significant bleeding n=86	1
Week 4, Any bleeding n=68	20
Week 4, Significant bleeding n=68	4
Week 5, Any bleeding n=61	21
Week 5, Significant bleeding n=61	4
Week 6, Any bleeding n=55	17
Week 6, Significant bleeding n=55	3
Week 7, Any bleeding n=52	14
Week 7, Significant bleeding n=52	1
Week 8, Any bleeding n=52	17
Week 8, Significant bleeding n=52	4
Week 9, Any bleeding n=45	11
Week 9, Significant bleeding n=45	1
Week 10, Any bleeding n=42	8
Week 10, Significant bleeding n=42	2
Week 11, Any bleeding n=40	12
Week 11, Significant bleeding n=40	3
Week 12, Any bleeding n=63	15
Week 12, Significant bleeding n=63	5
Week 13, Any bleeding n=30	9
Week 13, Significant bleeding n=30	2
Week 14, Any bleeding n=38	9
Week 14, Significant bleeding n=38	2
Week 15, Any bleeding n=43	10
Week 15, Significant bleeding n=43	2
Week 16, Any bleeding n=47	11
Week 16, Significant bleeding n=47	4
Week 17, Any bleeding n=37	10
Week 17, Significant bleeding n=37	2
Week 18, Any bleeding n=33	8
Week 18, Significant bleeding n=33	1
Week 19, Any bleeding n=44	15
Week 19, Significant bleeding n=44	2
Week 20, Any bleeding n=39	7
Week 20, Significant bleeding n=39	2
Week 21, Any bleeding n=41	10
Week 21, Significant bleeding n=41	2
Week 22, Any bleeding n=34	7
Week 22, Significant bleeding n=34	3
Week 23, Any bleeding n=36	15
Week 23, Significant bleeding n=36	2
Week 24, Any bleeding n=79	19
Week 24, Significant bleeding n=79	5
Follow-up Week 1, Any bleeding n=29	8
Follow-up Week 1, Significant bleeding n=29	2
Follow-up Week 2, Any bleeding n=37	25
Follow-up Week 2, Significant bleeding n=37	5
Follow-up Week 3, Any bleeding n=40	17
Follow-up Week 3, Significant bleeding n=40	5
Follow-up Week 4, Any bleeding n=70	23
Follow-up Week 4, Significant bleeding n=70	3
Any follow-up Week, Any bleeding n=77	38
Any Follow-up Week, Significant bleeding n=77	8

Notes
[24] - ITT population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.

End point type

Secondary

End point timeframe

From Day 1 of Treatment up to Week 13 of Part 1+ 1 day

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[25]	63 ^[26]
Units: Participants
number (not applicable)
Any AE	21	51
Any SAE	4	5

Notes
[25] - Safety Population: all participants who received at least one dose of the investigational product
[26] - Safety Population: all participants who received at least one dose of the investigational product

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening; requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.

End point type

Secondary

End point timeframe

From Day 1 of Part 2 up to Week 24 of Part 2 + 1 day

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[27]
Units: Participants
number (not applicable)
Any AE	69
Any SAE	9

Notes
[27] - Safety Population: all participants who received at least one dose of the investigational product

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Clinical chemistry parameters were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE), version 4.0: Grade 0(G0), none; Grade 1(G1), mild; Grade 2(G2), moderate; Grade 3(G3), severe; Grade 4(G4), life-threatening or disabling. Parameters included: aspartate amino transferase(AST), alkaline phosphatase(ALP), total bilirubin, albumin, alanine amino transferase(ALT), prothrombin international normalized ratio(PT INR), activated partial thromboplastin time(APTT), and creatinine. The BL value is defined as the value taken at Day 1 or, if missing, the latest non-missing Screening value. For serum creatinine, due to the variations in creatinine, the average of the Screening and the Day 1 values will be used as BL. The maximum post-BL toxicity grade includes any scheduled or unscheduled post-BL assessment during Part 1. Only participants available at the specified time points were analyzed(represented by n=X,X in the category titles)

End point type

Secondary

End point timeframe

From Baseline up to Week 13 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[28]	63 ^[29]
Units: Participants
number (not applicable)
AST, G0, n=29, 63	26	50
AST, G1, n=29, 63	3	12
AST, G2, n=29, 63	0	1
AST, G3, n=29, 63	0	0
AST, G4, n=29, 63	0	0
ALT, G0, n=29, 63	27	52
ALT, G1, n=29, 63	2	6
ALT, G2, n=29, 63	0	3
ALT, G3, n=29, 63	0	2
ALT, G4, n=29, 63	0	0
Total Bilirubin, G0, n=29, 63	29	60
Total Bilirubin, G1, n=29, 63	0	3
Total Bilirubin, G2, n=29, 63	0	0
Total Bilirubin, G3, n=29, 63	0	0
Total Bilirubin, G4, n=29, 63	0	0
Albumin, G0, n=29, 63	29	63
Albumin, G1, n=29, 63	0	0
Albumin, G2, n=29, 63	0	0
Albumin, G3, n=29, 63	0	0
Albumin, G4, n=29, 63	0	0
ALP, G0, n=29, 63	28	47
ALP, G1, n=29, 63	1	16
ALP, G2, n=29, 63	0	0
ALP, G3, n=29, 63	0	0
ALP, G4, n=29, 63	0	0
PT INR, G0, n=27, 58	26	57
PT INR, G1, n=27, 58	1	1
PT INR, G2, n=27, 58	0	0
PT INR, G3, n=27, 58	0	0
PT INR, G4, n=27, 58	0	0
APTT, G0 n=27, 58	13	24
APTT, G1, n=27, 58	13	32
APTT, G2, n=27, 58	1	2
APTT, G3, n=27, 58	0	0
APTT, G4, n=27, 58	0	0
Creatinine, G0, n=29, 63	22	47
Creatinine, G1, n=29, 63	7	15
Creatinine, G2, n=29, 63	0	1
Creatinine, G3, n=29, 63	0	0
Creatinine, G4, n=29, 63	0	0

Notes
[28] - Safety population
[29] - Safety population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Clinical chemistry parameters were summarized according to the NCI CTCAE, version 4.0: G0, none; G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Parameters included: AST, ALP, total bilirubin, albumin, ALT, and creatinine. For participants randomized to Placebo in Part 1, the BL value for Part 2 is defined as the value taken at Week 13 of Part 1. For serum creatinine, the value taken at Week 13 of Part 1 will be used as BL. For participants randomized to Eltrombopag in Part 1, the BL value is defined as the value taken on Day 1 or, if missing, the latest non-missing Screening value. For serum creatinine, due to the variations in creatinine, the average of the Screening and the Day 1 values will be used as BL. For participants who do not have both a Screening and Day 1 value, the Screening or Day 1 value will be used as BL. The maximum post-BL toxicity grade includes any scheduled or unscheduled post-BL assessment.

End point type

Secondary

End point timeframe

From Baseline (BL) of Part 2 through Follow-up

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[30]
Units: Participants
number (not applicable)
AST, G0	63
AST, G1	21
AST, G2	1
AST, G3	2
AST, G4	0
ALT, G0	67
ALT, G1	14
ALT, G2	3
ALT, G3	3
ALT, G4	0
Total Bilirubin, G0	80
Total Bilirubin, G1	4
Total Bilirubin, G2	3
Total Bilirubin, G3	0
Total Bilirubin, G4	0
Albumin, G0	85
Albumin, G1	1
Albumin, G2	1
Albumin, G3	0
Albumin, G4	0
ALP, G0	67
ALP, G1	20
ALP, G2	0
ALP, G3	0
ALP, G4	0
Creatinine, G0	72
Creatinine, G1	14
Creatinine, G2	1
Creatinine, G3	0
Creatinine, G4	0

Notes
[30] - Safety Population. Only participants who entered Part 2 (Open-label eltrombopag phase) were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Hematology parameters were summarized according to the NCI CTCAE, version 4.0: G0, none; G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Hematology parameters included: leukocytes, neutrophils, hemoglobin (increased), hemoglobin (anemia), lymphocytes (increased), and lymphocytes (decreased). The Baseline value is defined as the value taken at Day 1 or, if missing, the latest non-missing Screening value. The maximum post-Baseline toxicity grade includes any scheduled or unscheduled post-Baseline assessment during Part 1. Only those participants available at the specified time points were analyzed (represented by n=X,X in the category titles).

End point type

Secondary

End point timeframe

From Baseline up to Week 13 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[31]	63 ^[32]
Units: Participants
number (not applicable)
Leukocytes, G0, n=29, 63	23	50
Leukocytes, G1, n=29, 63	6	11
Leukocytes, G2, n=29, 63	0	0
Leukocytes, G3, n=29, 63	0	1
Leukocytes, G4, n=29, 63	0	1
Neutrophils G0, n=29, 63	27	52
Neutrophils G1, n=29, 63	1	3
Neutrophils G2, n=29, 63	0	6
Neutrophils G3, n=29, 63	1	0
Neutrophils G4, n=29, 63	0	2
Hemoglobin (increased), G0, n=29, 63	26	49
Hemoglobin (increased), G1, n=29, 63	3	12
Hemoglobin (increased), G2, n=29, 63	0	2
Hemoglobin (increased), G3, n=29, 63	0	0
Hemoglobin (increased), G4, n=29, 63	0	0
Hemoglobin (anemia), G0, n=29, 63	20	42
Hemoglobin (anemia), G1, n=29, 63	7	17
Hemoglobin (anemia), G2, n=29, 63	0	4
Hemoglobin (anemia), G3, n=29, 63	2	0
Hemoglobin (anemia), G4, n=29, 63	0	0
Lymphocytes (increased), G0, n=29, 63	17	37
Lymphocytes (increased), G1, n=29, 63	0	0
Lymphocytes (increased), G2, n=29, 63	12	26
Lymphocytes (increased), G3, n=29, 63	0	0
Lymphocytes (increased), G4, n=29, 63	0	0
Lymphocytes (decreased), G0, n=29, 63	25	48
Lymphocytes (decreased), G1, n=29, 63	4	13
Lymphocytes (decreased), G2, n=29, 63	0	1
Lymphocytes (decreased), G3, n=29, 63	0	1
Lymphocytes (decreased), G4, n=29, 63	0	0

Notes
[31] - Safety population
[32] - Safety population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Hematology parameters were summarized according to the NCI CTCAE, version 4.0: G0, none, G1, mild; G2, moderate; G3, severe; G4, life-threatening or disabling. Hematology parameters included: leukocytes, neutrophils, hemoglobin (increased), hemoglobin (anemia), lymphocytes (increased), and lymphocytes (decreased). For participants randomized to Placebo in Part 1, the BL value for Part 2 is defined as the value taken at Week 13 of Part 1. For participants randomized to Eltrombopag in Part 1, the BL value is defined as the value taken on Day 1 or, if missing, the latest non-missing Screening value. For participants who do not have both a Screening and Day 1 value, the Screening or Day 1 value will be used as BL. The maximum post-BL toxicity grade includes any scheduled or unscheduled post-BL assessment.

End point type

Secondary

End point timeframe

From Baseline up to Week 24 of Part 2 and Follow-up Weeks 1 to 4 (up to Study Week 41)

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[33]
Units: Participants
number (not applicable)
Leukocytes, G0	59
Leukocytes, G1	23
Leukocytes, G2	3
Leukocytes, G3	2
Leukocytes, G4	0
Neutrophils, G0	63
Neutrophils, G1	6
Neutrophils, G2	13
Neutrophils, G3	2
Neutrophils, G4	3
Hemoglobin (increased), G0	74
Hemoglobin (increased), G1	11
Hemoglobin (increased), G2	2
Hemoglobin (increased), G3	0
Hemoglobin (increased), G4	0
Hemoglobin (anemia), G0	48
Hemoglobin (anemia), G1	31
Hemoglobin (anemia), G2	7
Hemoglobin (anemia), G3	1
Hemoglobin (anemia), G4	0
Lymphocytes (increased), G0	47
Lymphocytes (increased), G1	0
Lymphocytes (increased), G2	40
Lymphocytes (increased), G3	0
Lymphocytes (increased), G4	0
Lymphocytes (decreased), G0	65
Lymphocytes (decreased), G1	19
Lymphocytes (decreased), G2	2
Lymphocytes (decreased), G3	1
Lymphocytes (decreased), G4	0

Notes
[33] - Safety Population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Vital sign measurements were taken before blood draws and included systolic blood pressure(SBP), diastolic blood pressure(DBP), and heart rate(HR). The number of par are reported with vital sign data falling outside the standard RR: RR high(RRH) and RR low(RRL). The BL value is the value taken at Day 1 or if missing, the latest non-missing SCR value. RR for SBP or DBP (mmHg) are read: Lower Limit of Normal, Normal Range, Upper Limit of Normal. For Ages 1 to 5 years (yrs) ranges are SBP <85, 85 to 115, >115; DBP <45, 45 to70, >70. Ages 6 to 11 yrs: SBP <85, 85 to 120, >120;, DBP <50, 50 to 75, >75. Ages 12 to 17 yrs: SBP <95, 95 to 135, >135; DBP <55, 55 to 85, >85. RR for HR(bpm) are ages 1 to < 3 yrs: <90, 90 to 140, >140; ages 3 to < 5 yrs: <75, 75 to 130, >130, ages 5 to < 8yrs: <65, 65 to 115, >115; ages 8 to < 12yrs: <55, 55 to 110, >110; and ages 12 to 18 yrs: <55, 55 to 110, >110. Only par available at the specified time points were analyzed( n=X,X in the category title)

End point type

Secondary

End point timeframe

From Screening (SCR) up to Week 13 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[34]	63 ^[35]
Units: Participants
number (not applicable)
DBP, Day 1, RRH, n=28,62	6	8
DBP, Day 1, RRL, n=28, 62	2	5
DBP, Week 1, RRH, n=28, 63	3	10
DBP, Week 1, RRL, n=28, 63	0	5
DBP, Week 2, RRH, n=29, 63	3	8
DBP, Week 2, RRL, n=29, 63	2	6
DBP, Week 3, RRH, n=28, 63	7	12
DBP, Week 3, RRL, n=28, 63	2	6
DBP, Week 4, RRH, n=29, 62	7	5
DBP, Week 4, RRL, n=29, 62	2	9
DBP, Week 5, RRH, n=27, 62	4	10
DBP, Week 5, RRL, n=27, 62	2	6
DBP, Week 6, RRH, n=28, 62	7	10
DBP, Week 6, RRL, n=28, 62	1	8
DBP, Week 7, RRH, n=28, 63	3	7
DBP, Week 7, RRL, n=28, 63	2	5
DBP, Week 8, RRH, n=28, 63	4	9
DBP, Week 8, RRL, n=28, 63	2	8
DBP, Week 9, RRH, n=27, 61	4	9
DBP, Week 9, RRL, n=27, 61	2	4
DBP, Week 10, RRH, n=28, 62	6	8
DBP, Week 10, RRL, n=28, 62	2	7
DBP, Week 11, RRH, n=28, 61	6	8
DBP, Week 11, RRL, n=28, 61	3	6
DBP, Week 12, RRH, n=28, 61	3	8
DBP, Week 12, RRL, n=28, 61	0	6
DBP, Week 13, RRH, n=28, 61	4	9
DBP, Week 13, RRL, n=28, 61	3	4
Heart Rate, Day 1, RRH, n=28, 62	0	2
Heart Rate, Day 1, RRL, n=28, 62	0	1
Heart Rate, Week 1, RRH, n=28, 63	0	0
Heart Rate, Week 1, RRL, n=28, 63	0	0
Heart Rate, Week 2, RRH, n=29, 63	2	1
Heart Rate, Week 2, RRL, n=29, 63	0	1
Heart Rate, Week 3, RRH, n=28, 63	1	2
Heart Rate, Week 3, RRL, n=28, 63	0	0
Heart Rate, Week 4, RRH, n=29, 61	0	4
Heart Rate, Week 4, RRL, n=29, 61	0	1
Heart Rate, Week 5, RRH, n=27, 62	1	5
Heart Rate, Week 5, RRL, n=27, 62	1	0
Heart Rate, Week 6, RRH, n=28,62	1	1
Heart Rate, Week 6, RRL, n=28, 62	1	0
Heart Rate, Week 7, RRH, n=28, 63	0	2
Heart Rate, Week 7, RRL, n=28, 63	1	0
Heart Rate, Week 8, RRH, n=28, 63	1	2
Heart Rate, Week 8, RRL, n=28, 63	1	0
Heart Rate, Week 9, RRH, n=27, 61	1	2
Heart Rate, Week 9, RRL, n=27, 61	0	0
Heart Rate, Week 10, RRH, n=28, 62	1	1
Heart Rate, Week 10, RRL, n=28, 62	0	0
Heart Rate, Week 11, RRH, n=28, 61	1	2
Heart Rate, Week 11, RRL, n=28, 61	0	0
Heart Rate, Week 12, RRH, n=28,61	0	2
Heart Rate, Week 12, RRL, n=28, 61	0	0
Heart Rate, Week 13, RRH, n=28, 61	0	3
Heart Rate, Week 13, RRL, n=28, 61	1	0
SBP, Day 1, RRH, n=28, 62	5	10
SBP, Day 1, RRL, n=28, 62	3	6
SBP, Week 1, RRH, n=28, 63	3	11
SBP, Week 1, RRL, n=28,63	4	8
SBP, Week 2, RRH, n=29, 63	4	7
SBP, Week 2, RRL, n=29, 63	3	9
SBP, Week 3, RRH, n=28, 63	3	9
SBP, Week 3, RRL, n=28, 63	2	9
SBP, Week 4, RRH, n=29, 62	3	10
SBP, Week 4, RRL, n=29, 62	2	9
SBP, Week 5, RRH, n=27, 62	5	9
SBP, Week 5, RRL, n=27, 62	4	7
SBP, Week 6, RRH, n=28, 62	5	7
SBP, Week 6, RRL, n=28, 62	3	8
SBP, Week 7, RRH, n=28, 63	5	10
SBP, Week 7, RRL, n=28, 63	3	7
SBP, Week 8, RRH, n=28, 63	3	14
SBP, Week 8, RRL, n=28, 63	4	7
SBP, Week 9, RRH, n=27, 61	4	12
SBP, Week 9, RRL, n=27, 61	3	7
SBP, Week 10, RRH, n=28, 62	4	11
SBP, Week 10, RRL, n=28, 62	3	11
SBP, Week 11, RRH, n=28, 61	6	12
SBP, Week 11, RRL, n=28, 61	5	9
SBP, Week 12, RRH, n=28, 61	4	11
SBP, Week 12, RRL, n=28, 61	4	4
SBP, Week 13, RRH, n=28, 61	6	9
SBP, Week 13, RRL, n=28, 61	4	7

Notes
[34] - Safety population
[35] - Safety population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Vital sign measurements were taken before any blood draw and included systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate(HR). The number of par are reported with vital sign data falling outside the standard RR as RR high(RRH) and RR low(RRL) from SCR up to Week 24 of Part 2 and from Follow-up Week 1 to Week 4. RR for Blood Pressure(mmHg) are read as: Lower Limit of Normal, Normal Range, Upper Limit of Normal. For Ages 1 to 5 years (yrs) ranges are SBP <85, 85 to 115, >115; DBP <45, 45 to70, >70. Ages 6 to 11 yrs: SBP <85, 85 to 120, >120; DBP <50, 50 to 75, >75. Ages 12 to 17 yrs: SBP <95, 95 to 135, >135; DBP <55, 55 to 85, >85. RR for HR (bpm) are ages 1 to < 3 yrs: <90, 90 to 140, >140; ages 3 to < 5 yrs: <75, 75 to 130, >130, ages 5 to < 8yrs: <65, 65 to 115, >115; ages 8 to < 12yrs: <55, 55 to 110, >110; and ages 12 to 18 yrs: <55, 55 to 110, >110. Only par available at the specified time points were analyzed (represented by n=X in the category titles)

End point type

Secondary

End point timeframe

From Week 1 up to Week 24 of Part 2 and Follow-up Week 1 to Week 4 (up to Week 41)

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[36]
Units: Participants
number (not applicable)
DBP, Week 1, RRH, n=87	14
DBP, Week 1, RRL, n=87	8
DBP, Week 2, RRH, n=86	14
DBP, Week 2, RRL, n=86	8
DBP, Week 3, RRH, n=86	13
DBP, Week 3, RRL, n=86	11
DBP, Week 4, RRH, n=68	10
DBP, Week 4, RRL, n=68	7
DBP, Week 5, RRH, n=61	7
DBP, Week 5, RRL, n=61	7
DBP, Week 6, RRH, n=55	6
DBP, Week 6, RRL, n=55	4
DBP, Week 7, RRH, n=52	7
DBP, Week 7, RRL, n=52	5
DBP, Week 8, RRH, n=53	4
DBP, Week 8, RRL, n=53	6
DBP, Week 9, RRH, n=45	3
DBP, Week 9, RRL, n=45	7
DBP, Week 10, RRH, n=42	5
DBP, Week 10, RRL, n=42	7
DBP, Week 11, RRH, n=40	5
DBP, Week 11, RRL, n=40	7
DBP, Week 12, RRH, n=63	9
DBP, Week 12, RRL, n=63	11
DBP, Week 13, RRH, n=29	4
DBP, Week 13, RRL, n=29	2
DBP, Week 14, RRH, n=38	2
DBP, Week 14, RRL, n=38	9
DBP, Week 15, RRH, n=43	7
DBP, Week 15, RRL, n=43	3
DBP, Week 16, RRH, n=47	3
DBP, Week 16, RRL, n=47	6
DBP, Week 17, RRH, n=37	5
DBP, Week 17, RRL, n=37	6
DBP, Week 18, RRH, n=34	7
DBP, Week 18, RRL, n=34	5
DBP, Week 19, RRH, n=44	5
DBP, Week 19, RRL, n=44	3
DBP, Week 20, RRH, n=39	6
DBP, Week 20, RRL, n=39	3
DBP, Week 21, RRH, n=41	9
DBP, Week 21, RRL, n=41	6
DBP, Week 22, RRH, n=34	6
DBP, Week 22, RRL, n=34	3
DBP, Week 23, RRH, n=36	6
DBP, Week 23, RRL, n=36	6
DBP, Week 24, RRH, n=79	14
DBP, Week 24, RRL, n=79	10
DBP, Follow-Up Week 1, RRH, n=29	8
DBP, Follow-Up Week 1, RRL, n=29	3
DBP, Follow-Up Week 2, RRH, n=37	8
DBP, Follow-Up Week 2, RRL, n=37	6
DBP, Follow-Up Week 3, RRH, n=39	4
DBP, Follow-Up Week 3, RRL, n=39	5
DBP, Follow-Up Week 4, RRH, n=67	8
DBP, Follow-Up Week 4, RRL, n=67	5
Heart Rate, Week 1, RRH, n=87	4
Heart Rate, Week 1, RRL, n=87	1
Heart Rate, Week 2, RRH, n=86	3
Heart Rate, Week 2, RRL, n=86	2
Heart Rate, Week 3, RRH, n=86	1
Heart Rate, Week 3, RRL, n=86	0
Heart Rate, Week 4, RRH, n=68	2
Heart Rate, Week 4, RRL, n=68	0
Heart Rate, Week 5, RRH, n=61	0
Heart Rate, Week 5, RRL, n=61	1
Heart Rate, Week 6, RRH, n=55	1
Heart Rate, Week 6, RRL, n=55	0
Heart Rate, Week 7, RRH, n=52	2
Heart Rate, Week 7, RRL, n=52	0
Heart Rate, Week 8, RRH, n=53	2
Heart Rate, Week 8, RRL, n=53	0
Heart Rate, Week 9, RRH, n=45	2
Heart Rate, Week 9, RRL, n=45	0
Heart Rate, Week 10, RRH, n=42	1
Heart Rate, Week 10, RRL, n=42	1
Heart Rate, Week 11, RRH, n=40	1
Heart Rate, Week 11, RRL, n=40	1
Heart Rate, Week 12, RRH, n=63	1
Heart Rate, Week 12, RRL, n=63	1
Heart Rate, Week 13, RRH, n=29	2
Heart Rate, Week 13, RRL, n=29	0
Heart Rate, Week 14, RRH, n=38	2
Heart Rate, Week 14, RRL, n=38	1
Heart Rate, Week 15, RRH, n=43	0
Heart Rate, Week 15, RRL, n=43	0
Heart Rate, Week 16, RRH, n=47	2
Heart Rate, Week 16, RRL, n=47	0
Heart Rate, Week 17, RRH, n=37	2
Heart Rate, Week 17, RRL, n=37	1
Heart Rate, Week 18, RRH, n=34	0
Heart Rate, Week 18, RRL, n=34	0
Heart Rate, Week 19, RRH, n=44	0
Heart Rate, Week 19, RRL, n=44	1
Heart Rate, Week 20, RRH, n=39	2
Heart Rate, Week 20, RRL, n=39	0
Heart Rate, Week 21, RRH, n=41	0
Heart Rate, Week 21, RRL, n=41	0
Heart Rate, Week 22, RRH, n=34	2
Heart Rate, Week 22, RRL, n=34	0
Heart Rate, Week 23, RRH, n=36	0
Heart Rate, Week 23, RRL, n=36	0
Heart Rate, Week 24, RRH, n=79	1
Heart Rate, Week 24, RRL, n=79	1
Heart Rate, Follow-Up Week 1, RRH, n=29	1
Heart Rate, Follow-Up Week 1, RRL, n=29	0
Heart Rate, Follow-Up Week 2, RRH, n=37	2
Heart Rate, Follow-Up Week 2, RRL, n=37	1
Heart Rate, Follow-Up Week 3, RRH, n=39	2
Heart Rate, Follow-Up Week 3, RRL, n=39	0
Heart Rate, Follow-Up Week 4, RRH, n=67	2
Heart Rate, Follow-Up Week 4, RRL, n=67	2
SBP, Week 1, RRH, n=87	13
SBP, Week 1, RRL, n=87	9
SBP, Week 2, RRH, n=86	19
SBP, Week 2, RRL, n=86	16
SBP, Week 3, RRH, n=86	15
SBP, Week 3, RRL, n=86	13
SBP, Week 4, RRH, n=68	10
SBP, Week 4, RRL, n=68	7
SBP, Week 5, RRH, n=61	7
SBP, Week 5, RRL, n=61	8
SBP, Week 6, RRH, n=55	11
SBP, Week 6, RRL, n=55	7
SBP, Week 7, RRH, n=52	10
SBP, Week 7, RRL, n=52	5
SBP, Week 8, RRH, n=53	8
SBP, Week 8, RRL, n=53	5
SBP, Week 9, RRH, n=45	8
SBP, Week 9, RRL, n=45	9
SBP, Week 10, RRH, n=42	4
SBP, Week 10, RRL, n=42	4
SBP, Week 11, RRH, n=40	4
SBP, Week 11, RRL, n=40	6
SBP, Week 12, RRH, n=63	14
SBP, Week 12, RRL, n=63	10
SBP, Week 13, RRH, n=29	3
SBP, Week 13, RRL, n=29	2
SBP, Week 14, RRH, n=38	5
SBP, Week 14, RRL, n=38	7
SBP, Week 15, RRH, n=43	9
SBP, Week 15, RRL, n=43	7
SBP, Week 16, RRH, n=47	7
SBP, Week 16, RRL, n=47	6
SBP, Week 17, RRH, n=37	9
SBP, Week 17, RRL, n=37	4
SBP, Week 18, RRH, n=34	6
SBP, Week 18, RRL, n=34	5
SBP, Week 19, RRH, n=44	7
SBP, Week 19, RRL, n=44	4
SBP, Week 20, RRH, n=39	5
SBP, Week 20, RRL, n=39	5
SBP, Week 21, RRH, n=41	10
SBP, Week 21, RRL, n=41	6
SBP, Week 22, RRH, n=34	6
SBP, Week 22, RRL, n=34	4
SBP, Week 23, RRH, n=36	6
SBP, Week 23, RRL, n=36	3
SBP, Week 24, RRH, n=79	13
SBP, Week 24, RRL, n=79	12
SBP, Follow-Up Week 1, RRH, n=29	5
SBP, Follow-Up Week 1, RRL, n=29	3
SBP, Follow-Up Week 2, RRH, n=37	5
SBP, Follow-Up Week 2, RRL, n=37	7
SBP, Follow-Up Week 3, RRH, n=39	9
SBP, Follow-Up Week 3, RRL, n=39	4
SBP, Follow-Up Week 4, RRH, n=67	9
SBP, Follow-Up Week 4, RRL, n=67	7

Notes
[36] - Safety population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed.

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Change in visual acuity results are presented as No (no change from Baseline), Not Clinically Significant (NCS), Improvement, and Worsening since Baseline. The Baseline value was obtained at the Screening Visit.

End point type

Secondary

End point timeframe

Baseline and Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	29 ^[37]	63 ^[38]
Units: Participants
number (not applicable)
No Change	22	47
NCS	4	8
Improvement	1	2
Worsening	0	1
Not Measured	2	5

Notes
[37] - Safety population
[38] - Safety population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Change in visual acuity results are presented as No Change, NCS, Improvement, and Worsening since Baseline. The Baseline value was obtained at the Screening Visit.

End point type

Secondary

End point timeframe

Baseline and Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[39]
Units: Participants
number (not applicable)
No Change	58
NCS	13
Improvement	3
Worsening	6
Not Measured	7

Notes
[39] - Safety population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed.

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Change in visual acuity results are presented as No Change, NCS, Improvement, and Worsening since Baseline. The Baseline value was obtained at the Screening Visit.

End point type

Secondary

End point timeframe

Baseline and Follow-Up Week 24 (Study Week 61)

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	87 ^[40]
Units: Participants
number (not applicable)
No Change	63
NCS	12
Improvement	9
Worsening	2
Not Measured	1

Notes
[40] - Safety population. Only participants who entered Part 2(Open-label eltrombopag phase) were analyzed.

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with worsening visual acuity due to cataracts at Week 12 of Part 1 are presented. Change due to cataracts is categorized as "Yes" or "No". Only those participants who had a result of ‘worsening’ in assessment of change of visual acuity at this timepoint were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 12 of Part 1

End point values	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag
Number of subjects analysed	0 ^[41]	1 ^[42]
Units: Participants
number (not applicable)
Yes		0
No		1

Notes
[41] - Safety population
[42] - Safety population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with worsening visual acuity due to cataracts at Week 24 of Part 2 are presented. Change due to cataracts is categorized as "Yes" or "No".

End point type

Secondary

End point timeframe

Baseline and Week 24 of Part 2

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	6 ^[43]
Units: Participants
number (not applicable)
Yes	1
No	5

Notes
[43] - Safety Population. Only participants who had worsening visual acuity at Week 24 were analyzed.

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with worsening visual acuity due to cataracts at Follow-up Week 24 are presented. Change due to cataracts is categorized as "Yes" or "No".

End point type

Secondary

End point timeframe

Baseline and Follow-Up Week 24 (Week 61)

End point values	Part 2 (Open-Label Period) - Eltrombopag
Number of subjects analysed	2 ^[44]
Units: Participants
number (not applicable)
Yes	0
No	2

Notes
[44] - Safety population. Only those participants who had worsening visual acuity at Week 61 were analyzed.

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. AUC(0-t) is defined as the area under the concentration-time curve over the dosing interval. The AUC(0-t) for a 50mg dose was estimated for each cohort. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.

End point type

Secondary

End point timeframe

Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)

End point values	Eltrombopag Cohort 1 (12-17 years)	Eltrombopag Cohort 2 (6-11 years)	Eltrombopag Cohort 3 (1-5 years)
Number of subjects analysed	33 ^[45]	38 ^[46]	19 ^[47]
Units: micrograms*hour per milliliter (ug.h/mL)
geometric mean (confidence interval 95%)	104 (86.1 to 126)	171 (147 to 200)	184 (147 to 230)

Notes
[45] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[46] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[47] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. CL/F is defined as the apparent oral clearance from plasma and Q/F is defined as apparent intercompartmental clearance. These parameters are dose independent. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort.

End point type

Secondary

End point timeframe

Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)

End point values	Eltrombopag Cohort 1 (12-17 years)	Eltrombopag Cohort 2 (6-11 years)	Eltrombopag Cohort 3 (1-5 years)
Number of subjects analysed	33 ^[48]	38 ^[49]	19 ^[50]
Units: Liters per hour (L/hr)
geometric mean (confidence interval 95%)
CL/F	0.48 (0.4 to 0.58)	0.29 (0.25 to 0.34)	0.19 (0.15 to 0.24)
Q/F	0.61 (0.54 to 0.68)	0.38 (0.34 to 0.42)	0.24 (0.2 to 0.28)

Notes
[48] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[49] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[50] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. Vc/F is defined as the volume of the central (e.g. plasma) compartment and Vp/F is defined as the volume of the peripheral compartment. These parameters are dose independent. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort.

End point type

Secondary

End point timeframe

PK Population. Only those participants who provided pharmacokinetic samples were analyzed

End point values	Eltrombopag Cohort 1 (12-17 years)	Eltrombopag Cohort 2 (6-11 years)	Eltrombopag Cohort 3 (1-5 years)
Number of subjects analysed	33 ^[51]	38 ^[52]	19 ^[53]
Units: Liters (L)
geometric mean (confidence interval 95%)
Vc/F	2.46 (2.2 to 2.75)	1.57 (1.35 to 1.81)	0.9 (0.76 to 1.05)
Vp/F	19.2 (17.7 to 20.9)	11.8 (10.9 to 12.9)	7.17 (6.58 to 7.81)

Notes
[51] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[52] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[53] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

End point type

Secondary

End point timeframe

Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)

End point values	Eltrombopag Cohort 1 (12-17 years)	Eltrombopag Cohort 2 (6-11 years)	Eltrombopag Cohort 3 (1-5 years)
Number of subjects analysed	33 ^[54]	38 ^[55]	19 ^[56]
Units: Units:1/h
number (not applicable)	0.189	0.189	0.189

Notes
[54] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[55] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[56] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed

No statistical analyses for this end point

Secondary: Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax

Top of page

End point title

Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax

End point description

Single PK samples were collected at each visit during Part 1 Weeks 2, 4, 6, 8, 10, 12 and at each weekly or monthly visit during Part 2 Weeks 1-12 (Study Weeks 13-37). The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. Cmax is defined as the maximum observed concentration. The Cmax for a 50mg dose was estimated for each cohort. From the final model, a single value of each PK parameter was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.

End point type

Secondary

End point timeframe

Part 1 Weeks 2, 4, 6, 8, 10, 12, and Part 2 Weeks 1-12 (Study Weeks 13 - 37)

End point values	Eltrombopag Cohort 1 (12-17 years)	Eltrombopag Cohort 2 (6-11 years)	Eltrombopag Cohort 3 (1-5 years)
Number of subjects analysed	33 ^[57]	38 ^[58]	19 ^[59]
Units: micrograms per milliliter (ug/mL)
geometric mean (confidence interval 95%)	6.94 (5.96 to 8.08)	11.2 (9.91 to 12.8)	12.5 (10.7 to 14.6)

Notes
[57] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[58] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed
[59] - PK Population. Only those participants who provided pharmacokinetic samples were analyzed

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

On-treatment adverse events (AEs) and serious adverse events (SAEs) are defined as events occuring from the start of investigational product until follow up (up to 61 weeks).

Adverse event reporting additional description

SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had received at least one dose of the investigational product.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Part 1 (Randomized Period)-Placebo

Reporting group description

Reporting group title

Part 1 (Randomized Period)-Eltrombopag

Reporting group description

Reporting group title

Part 2: Eltrombopag

Reporting group description

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

Serious adverse events	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag	Part 2: Eltrombopag
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 29 (13.79%)	5 / 63 (7.94%)	9 / 87 (10.34%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Investigations
Alanine aminotransferase abnormal
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase abnormal
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Haemorrhage
subjects affected / exposed	1 / 29 (3.45%)	0 / 63 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 29 (3.45%)	0 / 63 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Haemolytic anaemia
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	1 / 29 (3.45%)	0 / 63 (0.00%)	2 / 87 (2.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhinitis allergic
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Petechiae
subjects affected / exposed	1 / 29 (3.45%)	0 / 63 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Gingivitis
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia fungal
subjects affected / exposed	0 / 29 (0.00%)	1 / 63 (1.59%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematoma infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhinitis
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1 (Randomized Period)-Placebo	Part 1 (Randomized Period)-Eltrombopag	Part 2: Eltrombopag
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 29 (37.93%)	37 / 63 (58.73%)	56 / 87 (64.37%)
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 29 (0.00%)	4 / 63 (6.35%)	7 / 87 (8.05%)
occurrences all number	0	4	7
Alanine aminotransferase increased
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	6 / 87 (6.90%)
occurrences all number	0	0	6
Nervous system disorders
Headache
subjects affected / exposed	3 / 29 (10.34%)	6 / 63 (9.52%)	8 / 87 (9.20%)
occurrences all number	3	9	15
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 29 (3.45%)	4 / 63 (6.35%)	9 / 87 (10.34%)
occurrences all number	1	4	12
Influenza like illness
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	5 / 87 (5.75%)
occurrences all number	0	0	5
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 29 (0.00%)	6 / 63 (9.52%)	7 / 87 (8.05%)
occurrences all number	0	10	12
Vomiting
subjects affected / exposed	3 / 29 (10.34%)	2 / 63 (3.17%)	6 / 87 (6.90%)
occurrences all number	3	2	11
Diarrhoea
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	5 / 87 (5.75%)
occurrences all number	0	0	6
Abdominal pain upper
subjects affected / exposed	4 / 29 (13.79%)	3 / 63 (4.76%)	0 / 87 (0.00%)
occurrences all number	4	3	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	5 / 29 (17.24%)	8 / 63 (12.70%)	11 / 87 (12.64%)
occurrences all number	7	23	26
Cough
subjects affected / exposed	0 / 29 (0.00%)	7 / 63 (11.11%)	8 / 87 (9.20%)
occurrences all number	0	8	9
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 29 (6.90%)	11 / 63 (17.46%)	7 / 87 (8.05%)
occurrences all number	2	11	8
Rhinitis
subjects affected / exposed	2 / 29 (6.90%)	10 / 63 (15.87%)	0 / 87 (0.00%)
occurrences all number	2	11	0
Upper respiratory tract infection
subjects affected / exposed	1 / 29 (3.45%)	7 / 63 (11.11%)	9 / 87 (10.34%)
occurrences all number	1	8	10
Pharyngitis
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	7 / 87 (8.05%)
occurrences all number	0	0	7
Respiratory tract infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 63 (0.00%)	6 / 87 (6.90%)
occurrences all number	0	0	9

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

Secondary: Percentage of Responders

Secondary: Percentage of Responders

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

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

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

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

Secondary: Weighted mean platelet count

Secondary: Weighted mean platelet count

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax

Secondary: Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)