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Clinical Trial Results:
A three part, staggered cohort, open-label and double blind, randomized, placebo controlled study to investigate the efficacy, safety, tolerability and pharmacokinetics of eltrombopag, a thrombopoietin receptor agonist, in previously treated pediatric patients with chronic idiopathic thrombocytopenic purpura (ITP). Eltrombopag PETIT: Eltrombopag in PEdiatric patients with Thrombocytopenia from ITP Estudio abierto, doble ciego, aleatorizado, controlado con placebo, de cohortes escalonadas , con tres partes para investigar la eficacia, seguridad, tolerabilidad y farmacocinética de eltrombopag, un agonista del receptor de trombopoyetina, en pacientes pediátricos con púrpura trombocitopénica idiopática (PTI) crónica previamente tratados. Eltrombopag PETIT: Eltrombopag en pacientes pediátricos con trombocitopenia por PTI (Eltrombopag in PEdiatric patients with Thrombocytopenia from ITP)

Summary
EudraCT number	2006-002946-13
Trial protocol	ES GB FR NL Outside EU/EEA
Global end of trial date	03 Feb 2014

Results information
Results version number	v1(current)
This version publication date	13 Apr 2016
First version publication date	02 May 2015
Other versions

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

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Trial information

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Sponsor protocol code

TRA108062

ISRCTN number

US NCT number

NCT00908037

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,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343,

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000170-PIP01-07

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

03 Apr 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Feb 2014

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of eltrombopag, relative to placebo, in achieving a platelet count >=50Gi/L at any time during a 6 week treatment period when administered to previously treated pediatric subjects with chronic ITP.

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

30 Sep 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 16

Country: Number of subjects enrolled

United Kingdom: 11

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

United States: 44

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Canada: 8

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

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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.

Screening details

15 par were enrolled in a 24 Week(Wk) Open-Label(OL) eltrombopag Dose-Finding period(pd)(Part 1) then did not continue to Part 2 or 2/3. 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). All par entered a 4 WK follow-up pd, plus had a 3 and 6 month ocular follow-up.

Period 1 title

Part 1 and Part 2

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Part 1 was a non-randomized, controlled, Open-Label, dose finding period. Part 2 was a randomized, controlled, double blind period with blinding for the subject, investigator, monitor, data analyst, carer, and assessor.

Are arms mutually exclusive

Yes

Part 1 (Dose-Finding Period) Cohort 1

Arm description

Study Part 1 was a non-randomized, controlled, unblinded dose-finding period. 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 in Part 1 did not enter Parts 2 or 2/3.

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 12.5mg, 25mg, 50mg, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

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

Part 1 (Dose-Finding Period) Cohort 2

Arm description

Study Part 1 was a non-randomized, controlled, unblinded dose-finding period. 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 in Part 1 did not enter Parts 2 or 2/3.

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 12.5mg, 25mg, 50mg, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 1 (Dose-Finding Period) Cohort 3

Arm description

Study Part 1 was a non-randomized, controlled, unblinded dose-finding period. 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 in Part 1 did not enter Parts 2 or 2/3.

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 20mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

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

Part 2 (Randomized Period) Cohort 1-Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo to match eltrombopag 12.5, 25, 50, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2 (Randomized Period) Cohort 1-Eltrombopag

Arm description

Study Part 2 was randomized, controlled, with blinding for subject, investigator, monitor, data analyst, carer and assessor. 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 in Part 2 continued to Part 2/3.

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 12.5mg, 25mg, 50mg, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2 (Randomized Period) Cohort 2-Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo to match eltrombopag 12.5, 25, 50, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2 (Randomized Period) Cohort 2-Eltrombopag

Arm description

Study Part 2 was randomized, controlled, with blinding for subject, investigator, monitor, data analyst, carer and assessor. 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 in Part 2 continued to Part 2/3.

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 12.5mg, 25mg, 50mg, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2 (Randomized Period) Cohort 3-Placebo

Arm description

Arm type

Placebo

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

Part 2 (Randomized Period) Cohort 3-Eltrombopag

Arm description

Study Part 2 was randomized, controlled, with blinding for subject, investigator, monitor, data analyst, carer and assessor. 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. Participants in Part 2 continued to Part 2/3.

Arm type

Experimental

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 (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
Started	5	5	5	8	16	9	19	5	10
Completed	5	5	5	7	13	9	15	5	5
Not completed	0	0	0	1	3	0	4	0	5
Withdrawal by parent/ guardian	-	-	-	1	-	-	1	-	-
Lost to follow-up	-	-	-	-	2	-	-	-	4
Protocol deviation	-	-	-	-	1	-	3	-	1

Period 2 title

Part 2/3(Eltrombopag Open-Label Period)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Part 1 was a non-randomized, controlled, Open-Label, dose finding period. Particpants enrolled in Part 1 did not participate in Part 2. Part 2 was a randomized, controlled, double blind period with blinding for subject, investigator, monitor, data analyst, carer, and assessor. Part 2/3 was open-label, therefore no blinding was implemented.

Are arms mutually exclusive

Yes

Part 2/3 (Eltrombopag Open-Label Period) Cohort 1

Arm 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.

Arm type

Experimental

Investigational medicinal product name

Eltrombopag 12.5mg, 25mg, 50mg, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2/3 (Eltrombopag Open-Label Period) Cohort 2

Arm description

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.

Arm type

Experimental

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

Investigational medicinal product name

Eltrombopag 12.5mg, 25mg, 50mg, 75mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Part 2/3 (Eltrombopag Open- Label Period) Cohort 3

Arm description

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.

Arm type

Experimental

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 2/3 (Eltrombopag Open-Label Period) Cohort 1	Part 2/3 (Eltrombopag Open-Label Period) Cohort 2	Part 2/3 (Eltrombopag Open- Label Period) Cohort 3
Started	24	28	15
Completed	21	24	12
Not completed	3	4	3
Physician decision	1	-	-
Randomized but did not receive treatment	-	2	-
Adverse event, non-fatal	-	2	-
Lost to follow-up	1	-	2
Withdrawal by parent/guardian	1	-	-
Lack of efficacy	-	-	1

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: Participants enrolled in Part 1 did not enter Parts 2 or 2/3. Participants enrolled in Part 2 that completed treatment, continued to Part 2/3.

Baseline characteristics

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Reporting group title

Part 1 (Dose-Finding Period) Cohort 1

Reporting group description

Reporting group title

Part 1 (Dose-Finding Period) Cohort 2

Reporting group description

Reporting group title

Part 1 (Dose-Finding Period) Cohort 3

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 1-Placebo

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 1-Eltrombopag

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 2-Placebo

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 2-Eltrombopag

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 3-Placebo

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 3-Eltrombopag

Reporting group description

Reporting group values	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	Total
Number of subjects	5	5	5	8	16	9	19	5	10	82
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	14.2 ( 1.1 )	9.6 ( 1.14 )	3.6 ( 1.14 )	14.6 ( 1.69 )	13.7 ( 1.58 )	8.6 ( 2.24 )	8.2 ( 1.87 )	3.6 ( 1.34 )	3.3 ( 1.34 )	-
Gender categorical
Units: Subjects
Female	3	2	3	3	8	8	14	2	5	48
Male	2	3	2	5	8	1	5	3	5	34
Race/Ethnicity, Customized
Units: Subjects
African American/African Heritage	1	0	1	0	0	0	1	0	0	3
Asian - Japanese/East Asian Heritage	0	0	0	1	0	1	1	0	1	4
White - White/Caucasian/European	2	4	3	7	14	8	17	5	7	67
Unknown	1	0	0	0	0	0	0	0	0	1
White - Arabic/North African Heritage	0	0	0	0	1	0	0	0	1	2
Mixed Race	0	0	1	0	1	0	0	0	1	3
Asian - Central/South Asian Heritage	1	1	0	0	0	0	0	0	0	2

End points

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Reporting group title

Part 1 (Dose-Finding Period) Cohort 1

Reporting group description

Reporting group title

Part 1 (Dose-Finding Period) Cohort 2

Reporting group description

Reporting group title

Part 1 (Dose-Finding Period) Cohort 3

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 1-Placebo

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 1-Eltrombopag

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 2-Placebo

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 2-Eltrombopag

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 3-Placebo

Reporting group description

Reporting group title

Part 2 (Randomized Period) Cohort 3-Eltrombopag

Reporting group description

Reporting group title

Part 2/3 (Eltrombopag Open-Label Period) Cohort 1

Reporting group description

Reporting group title

Part 2/3 (Eltrombopag Open-Label Period) Cohort 2

Reporting group description

Reporting group title

Part 2/3 (Eltrombopag Open- Label Period) Cohort 3

Reporting group description

Subject analysis set title

Part 2 (Randomized Period) -Placebo

Subject analysis set type

Intention-to-treat

Subject analysis set 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.

Subject analysis set title

Part 2 (Randomized Period) -Eltrombopag

Subject analysis set type

Intention-to-treat

Subject analysis set 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 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.

Subject analysis set title

Eltrombopag Cohort 1- 12-17 Years

Subject analysis set type

Sub-group analysis

Subject analysis set 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.

Subject analysis set title

Eltrombopag Cohort 2 - 6-11 Years

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.

Subject analysis set title

Eltrombopag Cohort 3 - 1-5 Years

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.

Subject analysis set title

Part 1 (Dose-Finding Period)

Subject analysis set type

Safety analysis

Subject analysis set 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.

Subject analysis set title

Part 2 (Randomized Period) -Placebo

Subject analysis set type

Safety analysis

Subject analysis set 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.

Subject analysis set title

Part 2 (Randomized Period) -Eltrombopag

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Part 2/3 (Eltrombopag Open-Label Period)

Subject analysis set type

Safety analysis

Subject analysis set 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.

Subject analysis set title

Part 2 (Randomized Period) Cohort 2-Eltrombopag

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.

Subject analysis set title

Part 2 (Randomized Period) Cohort 3-Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged between 1 to 5 years received eltrombopag matching placebo administered as a dry powder for oral suspension QD for 7 weeks.

Subject analysis set title

Part 2 (Randomized Period) Cohort 3-Eltrombopag

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.

Primary: 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)

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End point 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) ^[1] ^[2]

End point 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. Intent-to-Treat (ITT) Population included all enrolled participants, those analyzed for this endpoint were enrolled 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.

End point type

Primary

End point timeframe

From Day 8 up to Day 43 of Part 2

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint only represents the percentage of participants from Part 2.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents percentage of participants from Part 2.

End point values	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
Number of subjects analysed	8	16	9	17	5	10
Units: Percentage of Participants
number (not applicable)	0	62.5	33.3	63.2	80	60

No statistical analyses for this end point

Secondary: 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)

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End point 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)

End point 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.

End point type

Secondary

End point timeframe

Between Day 15 and Day 43 of Part 2

End point values	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag
Number of subjects analysed	22 ^[3]	45 ^[4]
Units: Percentage of Participants
number (not applicable)	0	35.6

Notes
[3] - Intent-to-Treat(ITT) Population, only participants enrolled in Part 2 of this study were analyzed
[4] - Intent-to-Treat(ITT) Population, only participants enrolled in Part 2 of this study were analyzed

No statistical analyses for this end point

Secondary: Weighted Mean Platelet Count

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End point title

Weighted Mean Platelet Count

End point description

The weighted mean platelet count is defined as the area under the platelet-time curve divided by the duration of the 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 (BL) was defined as the platelet count taken on Day 1 or within 48 hours prior to the first dose of treatment.

End point type

Secondary

End point timeframe

Baseline and Day 43 of Part 2

End point values	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag
Number of subjects analysed	21 ^[5]	43 ^[6]
Units: Giga Cells Per Liter (Gi/L)
arithmetic mean (standard deviation)
Baseline (BL)	12.2 ( 8.59 )	15.5 ( 8.03 )
Day 43	30.5 ( 24.98 )	68 ( 56.78 )

Notes
[5] - ITT Population, only participants in Part 2 with a value at BL and post-BL were analyzed
[6] - ITT Population, only participants in Part 2 with a value at BL and post-BL were analyzed

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1

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End point title

Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1 ^[7]

End point 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.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Week 24 of Part 1

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the percentage of participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[8]	5 ^[9]	5 ^[10]
Units: Percentage of Participants
number (not applicable)	80	80	60

Notes
[8] - ITT Population only those participants enrolled during Part 1 were analyzed
[9] - ITT Population only those participants enrolled during Part 1 were analyzed
[10] - ITT Population only those participants enrolled during Part 1 were analyzed

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/3

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End point title

Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/3

End point 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 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. ITT Population. Only evaluable participants enrolled in Part 2/3 were included for this analysis, where participants with a baseline platelet count >10 Gi/L was considered as evaluable.

End point type

Secondary

End point timeframe

Part 2/3 up to Study Week 31

End point values	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
Number of subjects analysed	24 ^[11]	26 ^[12]	15 ^[13]
Units: Percentage of Participants
number (not applicable)	75	82.1	86.7

Notes
[11] - ITT Population only evaluable participants were included for this analysis
[12] - ITT Population only evaluable participants were included for this analysis
[13] - ITT Population only evaluable participants were included for this analysis

No statistical analyses for this end point

Secondary: Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3

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End point title

Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3

End point description

The area under the concentration-time curve over the dosing interval (AUC [0-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. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis and comprised the PK Population.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Study Week 31

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	29 ^[14]	30 ^[15]	19 ^[16]
Units: Microgramhour per milliliter (ugh/mL)
geometric mean (confidence interval 95%)	101 (87.1 to 117)	132 (114 to 152)	142 (117 to 173)

Notes
[14] - PK Population
[15] - PK Population
[16] - PK Population

No statistical analyses for this end point

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3

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End point title

Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3

End point 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. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Study Week 31

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	29 ^[17]	30 ^[18]	19 ^[19]
Units: micrograms per milliliter (ug/mL)
geometric mean (confidence interval 95%)
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 3.6)	2.91 (2.14 to 3.96)

Notes
[17] - PK Population
[18] - PK Population
[19] - PK Population

No statistical analyses for this end point

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3

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End point title

Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3

End point 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. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Study Week 31

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	29 ^[20]	30 ^[21]	19 ^[22]
Units: hour (hr)
median (full range (min-max))	4 (2 to 6)	4 (2 to 6)	2 (2 to 4)

Notes
[20] - PK Population
[21] - PK Population
[22] - PK Population

No statistical analyses for this end point

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3

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End point title

Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3

End point 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. All subjects who had received at least one dose of the investigational product and provided a PK sample were included in this analysis.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Study Week 31

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	29 ^[23]	30 ^[24]	19 ^[25]
Units: liter per hour (L/hr)
geometric mean (confidence interval 95%)	0.5 (0.43 to 0.57)	0.38 (0.33 to 0.44)	0.25 (0.2 to 0.3)

Notes
[23] - PK Population
[24] - PK Population
[25] - PK Population

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 7 Weeks of Eltrombopag Treatment in Part 2

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End point title

Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the 7 Weeks of Eltrombopag Treatment in Part 2 ^[26]

End point 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 up to Week 7 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. ITT Population, only those participants enrolled in Part 2 were analyzed. The number of participants used to compute the summary statistics reflect the ITT population through out the analyses during Part 2.

End point type

Secondary

End point timeframe

From Baseline through Week 7 of Part 2

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents data from participants from Part 2.

End point values	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
Number of subjects analysed	8 ^[27]	16 ^[28]	9 ^[29]	19 ^[30]	5 ^[31]	10 ^[32]
Units: Weeks
median (full range (min-max))	0 (0 to 0)	1 (0 to 5)	0 (0 to 2)	2 (0 to 6)	1 (0 to 2)	1 (0 to 6)

Notes
[27] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[28] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[29] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[30] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[31] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[32] - ITT Population, only participants enrolled in Part 2 of this study were analyzed

No statistical analyses for this end point

Secondary: Maximum Duration for Which a Participant (par) Continuously Maintained a Platelet Count of >=50 Gi/L During the 24 Weeks of Eltrombopag Treatment (trt) in Part 2/3

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End point title

Maximum Duration for Which a Participant (par) Continuously Maintained a Platelet Count of >=50 Gi/L During the 24 Weeks of Eltrombopag Treatment (trt) in Part 2/3

End point description

The maximum duration for which a par continuously maintained a platelet count >=50 Gi/L in the absence of rescue trt was calculated and summarized during the 24 wks of eltrombopag trt in Part 2/3. Par with non-weekly assessments were assumed to have maintained a positive response for each week(wk) between two assessments that had positive responses. If a par achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the par had achieved a positive response for one day. Par randomized to receive eltrombopag for 7 wks in Part 2 continued receiving eltrombopag for an additional 17 wks in Part 2/3(for a total of 24 wks of trt up to Study Wk 24. Par randomized to receive placebo for 7 wks in Part 2, received 24 wks of eltrombopag in Part 2/3(for a total of 24 weeks of trt) up to Study Wk 31. The number of par used to compute the summary statistics reflect the ITT population through out the analyses during Part 2/3.

End point type

Secondary

End point timeframe

From Baseline up to Study Week 31

End point values	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
Number of subjects analysed	24 ^[33]	28 ^[34]	15 ^[35]
Units: Weeks (wks)
median (full range (min-max))	2 (0 to 23)	8 (0 to 24)	4 (0 to 24)

Notes
[33] - ITT Population only those participants enrolled in Part 2/3 were analyzed.
[34] - ITT Population only those participants enrolled in Part 2/3 were analyzed.
[35] - ITT Population only those participants enrolled in Part 2/3 were analyzed.

No statistical analyses for this end point

Secondary: Percentage of Participants Who Reduced or Discontinued Baseline Concomitant Idiopathic Thrombocytopenic Purpura(ITP) Medications During the 24 Weeks of Eltrombopag Treatment During Part 1

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End point 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 ^[36]

End point 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.

End point type

Secondary

End point timeframe

From Baseline up to Week 24+ 1 day of Part 1

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents percentage of participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[37]	5 ^[38]	5 ^[39]
Units: Percentage of Participants
number (not applicable)
Taking an ITP medication at BL	0	20	0
Attempted red or dis	0	100	0
Permanent red or dis of all BL ITP medication	0	100	0
Permanent red or dis at least 1 BL ITP medication	0	100	0

Notes
[37] - ITT Population, only those participants enrolled during Part 1 were analyzed.
[38] - ITT Population, only those participants enrolled during Part 1 were analyzed.
[39] - ITT Population, only those participants enrolled during Part 1 were analyzed.

No statistical analyses for this end point

Secondary: Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/3

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End point title

Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/3

End point 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 (med) for at least one day during the period Part 2/3 Day 1 to the last dose of study medication + 1 day.

End point type

Secondary

End point timeframe

From Baseline to the end of treatment up to Week 31 + 1 day of Part 2/3

End point values	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
Number of subjects analysed	24 ^[40]	28 ^[41]	15 ^[42]
Units: Percentage of Participants
number (not applicable)
Taking an ITP medication at BL	25	17.9	13.3
Attempted red or dis	66.7	20	100
Permanent (perm) dis of all BL ITP	16.7	20	50
Perm dis at least 1 BL ITP med	33.3	20	50
Perm dis all BL ITP med taken prior to Part 2/3	0	40	0

Notes
[40] - ITT Population, only those participants enrolled during Part 2/3 were analyzed.
[41] - ITT Population, only those participants enrolled during Part 2/3 were analyzed.
[42] - ITT Population, only those participants enrolled during Part 2/3 were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3

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End point title

Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3

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. For participants 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 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.

End point type

Secondary

End point timeframe

From Baseline to the end of treatment up to Week 31 + 1 day of Part2/3

End point values	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
Number of subjects analysed	24 ^[43]	28 ^[44]	15 ^[45]
Units: Participants
number (not applicable)
New ITP Medication	8	4	4
Increase concomitant ITP medication from Baseline	1	0	0
Platelet transfusion	0	0	0
Splenectomy	0	0	0

Notes
[43] - ITT Population, only those participants enrolled during Part 2/3 were analyzed.
[44] - ITT Population, only those participants enrolled during Part 2/3 were analyzed.
[45] - ITT Population, only those participants enrolled during Part 2/3 were analyzed.

No statistical analyses for this end point

Secondary: 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

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End point 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 ^[46]

End point description

The KIT questionnaire measures the impact on the quality of life determined by the participant (par) 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 par under the age of six, the family questionnaire(parental proxy) has been used. Only par available at the specified time points were analyzed (represented by n=X,X,X in the category titles). Different par may have been analyzed at different time points, so the overall number of par analyzed reflects everyone in the ITT population.

End point type

Secondary

End point timeframe

Baseline, Week 6, Week 12, and Week 24 of Part 1

Notes
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the data from participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[47]	5 ^[48]	5 ^[49]
Units: Score on scale
arithmetic mean (standard deviation)
Baseline, n=5, 5, 5	73.18 ( 15.743 )	53.95 ( 16.534 )	74.8 ( 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 )	82.5 ( 15.995 )	78.87 ( 12.056 )

Notes
[47] - ITT Population, only those participants enrolled during Part 1 were analyzed
[48] - ITT Population, only those participants enrolled during Part 1 were analyzed
[49] - ITT Population, only those participants enrolled during Part 1 were analyzed

No statistical analyses for this end point

Secondary: Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2

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End point title

Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2 ^[50]

End point 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. 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.

End point type

Secondary

End point timeframe

Baseline and Week 6 of Part 2

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the data from participants from Part 2.

End point values	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
Number of subjects analysed	8 ^[51]	16 ^[52]	9 ^[53]	19 ^[54]	5 ^[55]	10 ^[56]
Units: Score on scale
arithmetic mean (standard deviation)
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 )

Notes
[51] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[52] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[53] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[54] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[55] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[56] - ITT Population, only participants enrolled in Part 2 of this study were analyzed

No statistical analyses for this end point

Secondary: 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

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End point 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

End point description

The KIT questionnaire measures the impact on the quality of life determined by the participant(par) 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 par under the age of six, the family questionnaire(parental proxy) has been used. Only those participants available at the specified time points were analyzed(represented by n=X,X,X in the category titles). Different par may have been analyzed at different time points, so the overall number of par analyzed reflects everyone in the ITT Population.

End point type

Secondary

End point timeframe

From Baseline to end of treatment up to Study Week 31

End point values	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
Number of subjects analysed	24 ^[57]	28 ^[58]	15 ^[59]
Units: Score on scale
arithmetic mean (standard deviation)
Baseline, n=17, 18, 10	79.34 ( 13.315 )	70.59 ( 16.237 )	79.1 ( 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 )	88.1 ( 11.166 )
Week 24, n=17, 11, 8	82.16 ( 16.926 )	83.93 ( 13.327 )	77.93 ( 22.971 )

Notes
[57] - ITT Population, only those participants enrolled in Part 2/3 were analyzed.
[58] - ITT Population, only those participants enrolled in Part 2/3 were analyzed.
[59] - ITT Population, only those participants enrolled in Part 2/3 were analyzed.

No statistical analyses for this end point

Secondary: 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

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End point 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 ^[60]

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=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. 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.

End point type

Secondary

End point timeframe

From Baseline through Week 7 of Part 2

Notes
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the number of participants from Part 2.

End point values	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
Number of subjects analysed	8 ^[61]	16 ^[62]	9 ^[63]	19 ^[64]	5 ^[65]	10 ^[66]
Units: Participants
number (not applicable)
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

Notes
[61] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[62] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[63] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[64] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[65] - ITT Population, only participants enrolled in Part 2 of this study were analyzed
[66] - ITT Population, only participants enrolled in Part 2 of this study were analyzed

No statistical analyses for this end point

Secondary: 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

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End point 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

End point description

End point type

Secondary

End point timeframe

From Baseline of Part 2/3 through Follow-up

End point values	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
Number of subjects analysed	24 ^[67]	28 ^[68]	15 ^[69]
Units: Participants
number (not applicable)
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

Notes
[67] - ITT Population, only those participants enrolled in Part 2/3 were analyzed.
[68] - ITT Population, only those participants enrolled in Part 2/3 were analyzed.
[69] - ITT Population, only those participants enrolled in Part 2/3 were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants With the Indicated Clinical Chemistry Parameter Falling Outside of the Reference Range (RR) Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

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End point title

Number of Participants With the Indicated Clinical Chemistry Parameter Falling Outside of the Reference Range (RR) Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

End point description

Clinical chemistry parameters included: aspartate amino transferase(AST, 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(RR:3-5 mmol/L), and sodium(RR:135-143 mmol/L). BL values were obtained at Day 1. The number of par with the indicated clinical chemistry data outside of the RR (high and low) any time post-BL are presented. Anytime post-BL assesments included any scheduled and unscheduled assessment. Only par available at the specified time points were analyzed(represented by n=X,X,X,X in the category titles). Different par may have been analyzed at different time points, so the overall number of par analyzed reflects the Safety Population

End point type

Secondary

End point timeframe

Post-Baseline (BL) from Week 1 through Follow-up up to Study Week 35

End point values	Part 1 (Dose-Finding Period)	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag	Part 2/3 (Eltrombopag Open-Label Period)
Number of subjects analysed	15 ^[70]	21 ^[71]	44 ^[72]	65 ^[73]
Units: Participants (par)
number (not applicable)
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
APTT, high, n=15, 21, 41, 63	4	2	1	11
APTT, 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

Notes
[70] - Safety Population
[71] - Safety Population
[72] - Safety Population
[73] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants (par) With the Indicated Hematology Parameters Falling Outside of the Reference Range (RR) at Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

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End point title

Number of Participants (par) With the Indicated Hematology Parameters Falling Outside of the Reference Range (RR) at Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

End point 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). BL values were obtained at Day 1. The number of par with the indicated hematology parameters data outside of the RR (with high and low) any time post-BL are presented. Anytime post-BL assesments included any scheduled and unscheduled post-BL assessment. Only those par available at the specified time points were analyzed (represented by n=X,X,X,X in the category titles). Different par may have been analyzed at different time points, so the overall number of par analyzed reflects everyone in the Safety Population.

End point type

Secondary

End point timeframe

Post-Baseline (BL) from Week 1 through Follow-up up to Study Week 35

End point values	Part 1 (Dose-Finding Period)	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag	Part 2/3 (Eltrombopag Open-Label Period)
Number of subjects analysed	15 ^[74]	21 ^[75]	44 ^[76]	65 ^[77]
Units: Participants
number (not applicable)
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

Notes
[74] - Safety Population
[75] - Safety Population
[76] - Safety Population
[77] - Safety Population

No statistical analyses for this end point

Secondary: 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

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End point 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

End point 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 assessments included any scheduled and unscheduled post-baseline assessment. 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.

End point type

Secondary

End point timeframe

Post-Baseline from Week 1 through Follow-up up to Study Week 35

End point values	Part 1 (Dose-Finding Period)	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag	Part 2/3 (Eltrombopag Open-Label Period)
Number of subjects analysed	15 ^[78]	21 ^[79]	44 ^[80]	65 ^[81]
Units: Participants
number (not applicable)
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

Notes
[78] - Safety Population.
[79] - Safety Population.
[80] - Safety Population.
[81] - Safety Population.

No statistical analyses for this end point

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1

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End point title

Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1 ^[82]

End point description

End point type

Secondary

End point timeframe

From Baseline up to Study Week 24 of Part 1

Notes
[82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the number of participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[83]	5 ^[84]	5 ^[85]
Units: Participants
number (not applicable)
Epithelial Renal Cell Casts	0	0	2
RBC Casts	0	0	0
WBC Casts	0	0	0

Notes
[83] - Safety Population, only those participants enrolled during Part 1 were analyzed.
[84] - Safety Population, only those participants enrolled during Part 1 were analyzed.
[85] - Safety Population, only those participants enrolled during Part 1 were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2

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End point title

Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2 ^[86]

End point description

End point type

Secondary

End point timeframe

From Baseline and post-Baseline up to Study Week 7 of Part 2

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the number of participants from Part 2.

End point values	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
Number of subjects analysed	8 ^[87]	16 ^[88]	9 ^[89]	17 ^[90]	4 ^[91]	11 ^[92]
Units: Participants
number (not applicable)
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

Notes
[87] - Safety Population, only those participants enrolled during Part 2 were analyzed.
[88] - Safety Population, only those participants enrolled during Part 2 were analyzed.
[89] - Safety Population, only those participants enrolled during Part 2 were analyzed.
[90] - Safety Population, only those participants enrolled during Part 2 were analyzed.
[91] - Safety Population, only those participants enrolled during Part 2 were analyzed.
[92] - Safety Population, only those participants enrolled during Part 2 were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3

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End point title

Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3

End point 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.

End point type

Secondary

End point timeframe

From Baseline and post-Baseline up to Study Week 31 of Part 2/3

End point values	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
Number of subjects analysed	24 ^[93]	26 ^[94]	15 ^[95]
Units: Participants
number (not applicable)
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

Notes
[93] - Safety Population, only those participants enrolled during Part 2/3 were analyzed.
[94] - Safety Population, only those participants enrolled during Part 2/3 were analyzed.
[95] - Safety Population, only those participants enrolled during Part 2/3 were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants (par) With the Indicated Vital Signs Falling Outside of the Reference Range (RR) During Part 1, Part 2, and Part 2/3

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End point title

Number of Participants (par) With the Indicated Vital Signs Falling Outside of the Reference Range (RR) During Part 1, Part 2, and Part 2/3

End point description

Vital sign assessments included systolic blood pressure(SBP) and diastolic blood pressure(DBP) measurements(millimeteres of mercury[mmHg]) taken before any blood draw at the indicated time points: Screening, Day 1, each WK from Week 1 to 24, each Follow-up WK(WK 1-4) and the maximum post-BL visit(MPB). BL is defined as the value obtained on Day 1 of treatment. The MPB included any scheduled or unscheduled post-BL assessment. RR for SBP(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 for Cohort 1: <45, 45-70,>70; for Cohort 2: <50, 50-75, >75; and Cohort 3: <55, 55-85, >85. Only par available at the specified time points were analyzed(represented by n=X,X,X,X in the category titles). Different par may have been analyzed at different time points, so the number analyzed reflects everyone in the Safety Population. Data values of 99999 indicate no par were analyzed, or "NA".

End point type

Secondary

End point timeframe

From Baseline (BL) through Study Week (WK) 35

End point values	Part 1 (Dose-Finding Period)	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag	Part 2/3 (Eltrombopag Open-Label Period)
Number of subjects analysed	15 ^[96]	21 ^[97]	44 ^[98]	65 ^[99]
Units: Participants
number (not applicable)
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	99999	99999	4
Week 8, DBP,low,n=15, 0, 0, 49	1	99999	99999	6
Week 9, DBP, high, n=15, 0, 0, 45	2	99999	99999	4
Week 9, DBP, low, n=15, 0, 0, 45	1	99999	99999	6
Week 10, DBP, high, n=15, 0, 0, 40	0	99999	99999	6
Week 10, DBP, low, n=15, 0, 0, 40	0	99999	99999	3
Week 11, DBP, high, n=13, 0, 0, 41	0	99999	99999	4
Week 11, DBP, low, n=13, 0, 0, 41	2	99999	99999	3
Week 12, DBP, high, n=13, 0, 0, 42	0	99999	99999	5
Week 12, DBP, low, n=13, 0, 0, 42	3	99999	99999	3
Week 13, DBP, high, n=12, 0, 0, 32	0	99999	99999	0
Week 13, DBP, low, n=12, 0, 0, 32	0	99999	99999	5
Week 14, DBP, high, n=9, 0, 0, 32	0	99999	99999	3
Week 14, DBP, low, n=9, 0, 0, 32	1	99999	99999	3
Week 15, DBP, high, n=11, 0, 0, 31	1	99999	99999	3
Week 15, DBP, low, n=11, 0, 0, 31	2	99999	99999	0
Week 16, DBP,high,n=12, 0, 0, 39	0	99999	99999	2
Week 16, DBP,low,n=12, 0, 0, 39	0	99999	99999	3
Week 17, DBP,high,n=5, 0, 0, 29	0	99999	99999	2
Week 17, DBP,low,n=5, 0, 0, 29	1	99999	99999	1
Week 18, DBP,high,n=9, 0, 0, 32	0	99999	99999	3
Week 18, DBP,low,n=9, 0, 0, 32	1	99999	99999	1
Week 19, DBP,high,n=5, 0, 0, 34	0	99999	99999	1
Week 19, DBP,low,n=5, 0, 0, 34	0	99999	99999	2
Week 20, DBP,high,n=13, 0, 0, 33	0	99999	99999	2
Week 20, DBP,low,n=13, 0, 0, 33	0	99999	99999	1
Week 21, DBP,high,n=10, 0, 0, 17	1	99999	99999	1
Week 21, DBP,low,n=10, 0, 0, 17	1	99999	99999	1
Week 22, DBP,high,n=11, 0, 0, 23	1	99999	99999	1
Week 22, DBP,low,n=11, 0, 0, 23	1	99999	99999	0
Week 23, DBP,high,n=11, 0, 0, 21	0	99999	99999	1
Week 23, DBP,low,n=11, 0, 0, 21	2	99999	99999	2
Week 24 DBP,high,n=15, 0, 0, 58	0	99999	99999	5
Week 24, DBP,low,n=15, 0, 0, 58	3	99999	99999	3
FU Week 1, DBP,high,n=5, 0, 0, 13	1	99999	99999	2
FU Week 1, DBP,low,n=5, 0, 0, 13	1	99999	99999	1
FU Week 2, DBP,high,n=5, 0, 0, 21	0	99999	99999	2
FU Week 2, DBP,low,n=5, 0, 0, 21	0	99999	99999	1
FU Week 3, DBP,high,n=5, 0, 0, 14	0	99999	99999	2
FU Week 3, DBP,low,n=5, 0, 0, 14	0	99999	99999	0
FU Week 4, DBP,high,n=3, 0, 0, 31	0	99999	99999	7
FU Week 4, DBP,low,n=3, 0, 0, 31	1	99999	99999	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	99999	99999	16
Week 8, SBP,low,n=15, 0, 0, 49	4	99999	99999	4
Week 9, SBP,high,n=15, 0, 0, 45	4	99999	99999	15
Week 9, SBP,low,n=15, 0, 0, 45	3	99999	99999	2
Week 10, SBP,high,n=15, 0, 0, 40	2	99999	99999	10
Week 10, SBP,low,n=15, 0, 0, 40	2	99999	99999	3
Week 11, SBP,high,n=13, 0, 0, 41	4	99999	99999	9
Week 11, SBP,low,n=13, 0, 0, 41	2	99999	99999	2
Week 12, SBP,high,n=13, 0, 0, 42	3	99999	99999	10
Week 12, SBP,low,n=13, 0, 0, 42	3	99999	99999	3
Week 13, SBP,high,n=12, 0, 0, 32	3	99999	99999	8
Week 13, SBP,low,n=12, 0, 0, 32	2	99999	99999	3
Week 14, SBP,high,n=9, 0, 0, 32	4	99999	99999	10
Week 14, SBP,low,n=9, 0, 0, 32	0	99999	99999	3
Week 15, SBP,high,n=11, 0, 0, 31	3	99999	99999	9
Week 15, SBP,low,n=11, 0, 0, 31	2	99999	99999	1
Week 16 SBP,high,n=12, 0, 0, 39	5	99999	99999	14
Week 16, SBP,low,n=12, 0, 0, 39	1	99999	99999	1
Week 17, SBP,high,n=5, 0, 0, 29	1	99999	99999	9
Week 17, SBP,low,n=5, 0, 0, 29	1	99999	99999	0
Week 18, SBP,high,n=9, 0, 0, 32	2	99999	99999	10
Week 18, SBP,low,n=9, 0, 0, 32	0	99999	99999	1
Week 19, SBP,high,n=5, 0, 0, 34	2	99999	99999	9
Week 19, SBP,low,n=5, 0, 0, 34	0	99999	99999	2
Week 20, SBP,high,n=13, 0, 0, 33	6	99999	99999	10
Week 20, SBP,low,n=13, 0, 0, 33	2	99999	99999	1
Week 21, SBP,high,n=10, 0, 0, 17	2	99999	99999	0
Week 21, SBP,low,n=10, 0, 0, 17	3	99999	99999	0
Week 22, SBP,high,n=11, 0, 0, 23	2	99999	99999	8
Week 22, SBP,low,n=11, 0, 0, 23	3	99999	99999	0
Week 23, SBP,high,n=11, 0, 0, 21	2	99999	99999	6
Week 23, SBP,low,n=11, 0, 0, 21	2	99999	99999	1
Week 24, SBP,high,n=15, 0, 0, 58	4	99999	99999	19
Week 24, SBP, low, n=15, 0, 0, 58	2	99999	99999	2
FU Week 1, SBP, high,n=5, 0, 0, 13	0	99999	99999	4
FU Week 1, SBP, low,n=5, 0, 0, 13	2	99999	99999	0
FU Week 2, SBP, high,n=5, 0, 0, 21	2	99999	99999	3
FU Week 2, SBP, low,n=5, 0, 0, 21	0	99999	99999	3
FU Week 3, SBP, high,n=5, 0, 0, 14	1	99999	99999	4
FU Week 3, SBP, low,n=5, 0, 0, 14	0	99999	99999	0
FU Week 4, SBP, high,n=3, 0, 0, 31	1	99999	99999	10
FU Week 4, SBP,low,n=3, 0, 0, 31	1	99999	99999	3

Notes
[96] - Safety Population, only par available at specified time points were analyzed. 99999 indicates NA
[97] - Safety Population, only par available at specified time points were analyzed. 99999 indicates NA.
[98] - Safety Population, only par available at specified time points were analyzed. 99999 indicates NA
[99] - Safety Population, only par available at specified time points were analyzed. 99999 indicates NA

No statistical analyses for this end point

Secondary: Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1

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End point title

Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1 ^[100]

End point 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. 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. Data values of 99999 indicate where no participants were analyzed at the specified time point, or there were too few participants analyzed so a standard deviation could not be calculated; therefore, no value is available, or "NA".

End point type

Secondary

End point timeframe

From Baseline through Week 24

Notes
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents data from participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[101]	5 ^[102]	5 ^[103]
Units: Breaths per min
arithmetic mean (standard deviation)
BL, n=4, 5, 4	20 ( 0 )	21.4 ( 4.1 )	25.5 ( 4.43 )
Week 1, n=4, 5, 4	21.5 ( 4.43 )	22 ( 6 )	26.5 ( 6.4 )
Week 2, n=5, 5, 4	20.6 ( 3.44 )	19.4 ( 4.98 )	24 ( 5.42 )
Week 3, n=5, 5, 5	22 ( 5.66 )	17 ( 5.1 )	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 ( 1.1 )	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 ( 2 )
Week 10, n=5, 5, 5	19.6 ( 2.61 )	18 ( 4 )	22.4 ( 1.67 )
Week 11, n=5, 3, 4	19.6 ( 1.67 )	20.3 ( 3.21 )	25 ( 5.03 )
Week 12, n=4, 3, 4	19.5 ( 1 )	20 ( 0 )	27.6 ( 11.52 )
Week 13, n=4, 4, 4	19.5 ( 1 )	21 ( 2.16 )	23 ( 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 ( 2 )	21.3 ( 1.15 )	24 ( 2 )
Week 16, n=5, 3, 4	18.8 ( 3.35 )	20 ( 4 )	30.8 ( 16.88 )
Week 17, n=2, 0, 3	18 ( 0 )	99999 ( 99999 )	24 ( 4 )
Week 18, n=3, 3, 4	19.3 ( 1.15 )	21.3 ( 3.06 )	29 ( 13.22 )
Week 19, n=3, 0, 2	19.3 ( 1.15 )	99999 ( 99999 )	28 ( 11.31 )
Week 20, n=5, 4, 4	19.6 ( 1.67 )	21.5 ( 3 )	23.5 ( 3.42 )
Week 21, n=3, 2, 5	19.3 ( 1.15 )	19 ( 1.41 )	23.6 ( 3.51 )
Week 22, n=3, 4, 3	19.3 ( 2.31 )	21 ( 2 )	27.3 ( 7.57 )
Week 23, n=4, 2, 4	20 ( 1.63 )	20 ( 0 )	21.5 ( 1.91 )
Week 24, n=5, 5, 4	19.6 ( 0.89 )	23 ( 3.16 )	24.8 ( 7.09 )
FU Week 1, n=1,1,3	20 ( 99999 )	20 ( 99999 )	22 ( 2 )
FU Week 2, n=3,2,0	19.3 ( 1.15 )	26.5 ( 9.19 )	99999 ( 99999 )
FU Week 3, n=2,1,2	21 ( 4.24 )	28 ( 99999 )	24.5 ( 4.95 )
FU Week 4, n=1,0,1	18 ( 99999 )	99999 ( 99999 )	24 ( 99999 )
MPB, n=5, 5, 5	24.4 ( 4.56 )	29.8 ( 6.02 )	32.2 ( 13.9 )

Notes
[101] - Safety Population
[102] - Safety Population
[103] - Safety Population

No statistical analyses for this end point

Secondary: Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2

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End point title

Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2 ^[104]

End point description

End point type

Secondary

End point timeframe

From Week 1 to Week 7 of Part 2

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the data from participants from Part 2.

End point values	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
Number of subjects analysed	8 ^[105]	16 ^[106]	9 ^[107]	17 ^[108]	4 ^[109]	11 ^[110]
Units: Breaths per min
arithmetic mean (standard deviation)
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 ( 1 )	18.8 ( 1.76 )	19.9 ( 2.26 )	20.7 ( 4.48 )	19 ( 1.41 )	28.2 ( 9.54 )
Week 2, n=6, 15, 9, 16, 4, 10	19.3 ( 2.73 )	18.9 ( 2.7 )	19.8 ( 2.33 )	23 ( 8.01 )	21.5 ( 5 )	27.1 ( 11.7 )
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 ( 2.58 )	25.8 ( 7.17 )
Week 4, n=7, 16, 8, 14, 4, 10	19.4 ( 2.51 )	18.6 ( 2.8 )	19.8 ( 2.49 )	21.4 ( 4.29 )	21.5 ( 1 )	25.4 ( 7.18 )
Week 5, n=8, 16, 8, 15, 3, 8	19.3 ( 1.04 )	18.5 ( 2.1 )	20.5 ( 2.98 )	19.7 ( 2.74 )	20 ( 2 )	29 ( 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 ( 1.15 )	24.4 ( 6.69 )
Week 7, n=7, 16, 9, 17, 4, 8	20.9 ( 2.27 )	18.4 ( 1.5 )	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 ( 2.18 )	22.7 ( 2.45 )	26.6 ( 7.87 )	23.5 ( 3.42 )	30 ( 13.39 )

Notes
[105] - Safety Population.
[106] - Safety Population.
[107] - Safety Population.
[108] - Safety Population.
[109] - Safety Population.
[110] - Safety Population.

No statistical analyses for this end point

Secondary: Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3

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End point title

Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3

End point 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. 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.

End point type

Secondary

End point timeframe

From Week 1 to Follow-up Week 4 of Part 2/3 up to Study Week 35

End point values	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
Number of subjects analysed	24 ^[111]	26 ^[112]	15 ^[113]
Units: Breaths per minute
arithmetic mean (standard deviation)
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 )	21.2 ( 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 ( 4.4 )	24 ( 6.09 )
Week 4, n=23, 23, 13	19 ( 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 ( 2.3 )	20.6 ( 4.11 )	23.3 ( 4.92 )
Week 7, n=22, 25, 11	18.8 ( 1.99 )	20.1 ( 4.46 )	22.4 ( 4.6 )
Week 8, n=19, 19, 10	19.2 ( 2.32 )	23.4 ( 6.23 )	22 ( 1.79 )
Week 9, n=17, 16, 12	19.5 ( 2.96 )	22 ( 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 ( 1.9 )	22.2 ( 3.76 )	23.6 ( 4.98 )
Week 13, n=11, 13, 8	19.3 ( 1.56 )	23.4 ( 7.68 )	21 ( 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	18.8 ( 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 ( 2.08 )	22.4 ( 6.45 )	25.2 ( 9.65 )
Week 18, n=16, 12, 4	19.1 ( 3.79 )	22 ( 4.53 )	29 ( 10.52 )
Week 19, n=14, 13, 6	18.1 ( 1.49 )	24.5 ( 19.33 )	24 ( 6.45 )
Week 20, n=13, 13, 7	17.4 ( 1.94 )	20.9 ( 3.52 )	33 ( 16.77 )
Week 21, n=4, 10, 3	18.8 ( 3.4 )	20.2 ( 3.55 )	28 ( 10.58 )
Week 22, n=11, 7, 5	19.7 ( 2.94 )	19.1 ( 2.79 )	26 ( 4.9 )
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 ( 1.6 )	20 ( 3.41 )	26 ( 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 ( 1.67 )	23 ( 4.16 )	24.8 ( 5.5 )
FU Week 4, n=10, 12, 7	19.4 ( 0.97 )	20.8 ( 1.86 )	21 ( 3.74 )
MPB, n=24, 26, 15	23 ( 2.78 )	27.7 ( 13 )	27.7 ( 11.54 )

Notes
[111] - Safety Population
[112] - Safety Population
[113] - Safety Population

No statistical analyses for this end point

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1

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End point title

Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1 ^[114]

End point 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. 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. Data values of 99999 indicate where no participants were analyzed at the specified time point or there were too few participants available to calculate a standard deviation; therefore, no value is available, or "NA".

End point type

Secondary

End point timeframe

From Week 1 to Follow-up Week 4 of Part 1, up to Study Week 28

Notes
[114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the data from participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[115]	5 ^[116]	5 ^[117]
Units: Beats per minute
arithmetic mean (standard deviation)
Screening, n=5, 5, 5	85.2 ( 15.71 )	88.4 ( 8.5 )	102 ( 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 ( 11.1 )
Week 4, n=5, 5, 5	86.4 ( 10.92 )	84 ( 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 ( 10.5 )	89.8 ( 13.79 )	103 ( 8.29 )
Week 7, n=5, 5, 5	82 ( 9.46 )	96.2 ( 17.84 )	103.2 ( 8.93 )
Week 8, n=5, 5, 5	83 ( 5.2 )	89.4 ( 15.04 )	111.8 ( 10.62 )
Week 9, n=5, 5, 5	80.4 ( 13.35 )	79.2 ( 11.34 )	101.5 ( 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 ( 16.5 )	106.6 ( 11.19 )
Week 12, n=4, 4, 5	80.5 ( 12.07 )	92 ( 12.83 )	101.4 ( 16.62 )
Week 13, n=4, 4, 4	90.8 ( 15.52 )	86.5 ( 7.05 )	103.8 ( 3.5 )
Week 14, n=3, 3, 3	81 ( 9.85 )	87 ( 8.66 )	101 ( 11 )
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 ( 18.6 )	103 ( 5.57 )	93 ( 18.96 )
Week 17, n=2, 0, 3	67.5 ( 20.51 )	99999 ( 99999 )	97.7 ( 12.01 )
Week 18, n=3, 3, 4	88 ( 10.44 )	86.7 ( 17.01 )	102.8 ( 16.88 )
Week 19, n=3, 0, 2	88 ( 20.81 )	99999 ( 99999 )	94 ( 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 ( 6.93 )	75.5 ( 3.54 )	101 ( 18.63 )
Week 22, n=3, 4, 4	70.3 ( 14.36 )	86.5 ( 9.04 )	100 ( 13.14 )
Week 23, n=4, 2, 5	71.5 ( 13.03 )	82.5 ( 3.54 )	96.2 ( 18.93 )
Week 24, n=5, 5, 5	79.6 ( 7.86 )	85.8 ( 6.91 )	96 ( 4.74 )
FU Week 1, n=1, 1, 3	81 ( 99999 )	125 ( 99999 )	107.7 ( 10.79 )
FU Week 2, n=3, 2, 0	77.7 ( 8.74 )	84.5 ( 28.99 )	99999 ( 99999 )
FU Week 3, n=2, 1, 2	87 ( 2.83 )	78 ( 99999 )	98 ( 8.49 )
FU Week 4, n=1, 0, 2	89 ( 99999 )	99999 ( 99999 )	99 ( 26.87 )
MBP, n=5, 5, 5	108.8 ( 24.01 )	109.8 ( 14.17 )	119.6 ( 5.73 )

Notes
[115] - Safety Population
[116] - Safety Population
[117] - Safety Population

No statistical analyses for this end point

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2

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End point title

Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2 ^[118]

End point description

End point type

Secondary

End point timeframe

From Week 1 to Week 7 of Part 2

Notes
[118] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the data from participants from Part 2.

End point values	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
Number of subjects analysed	8 ^[119]	16 ^[120]	9 ^[121]	17 ^[122]	4 ^[123]	11 ^[124]
Units: Beats per minute
arithmetic mean (standard deviation)
Screening, n=8, 16, 9, 15, 4, 11	80.1 ( 10.11 )	82.8 ( 17.28 )	86.9 ( 16.1 )	94.3 ( 17.53 )	91.5 ( 6.56 )	101.5 ( 23.48 )
Day 1, n=6, 14, 9, 13, 3, 11	77.2 ( 12.32 )	81.3 ( 8.7 )	93 ( 14.04 )	88.8 ( 12.84 )	98.7 ( 5.69 )	99.6 ( 15.84 )
Week 1, n=8, 16, 9, 17, 2, 11	76.4 ( 8.5 )	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, 4, 11	79.4 ( 8.75 )	81.7 ( 9.79 )	89 ( 12.44 )	91.8 ( 16.96 )	95.3 ( 7.09 )	102.5 ( 11.81 )
Week 3, n=8, 16, 9, 16, 4, 9	81.5 ( 12.21 )	84 ( 10.93 )	86.6 ( 13.39 )	95.8 ( 13.57 )	97 ( 14.67 )	102.6 ( 17.44 )
Week 4, n=8, 16, 9, 16, 4, 10	76.3 ( 6.96 )	82.4 ( 10.39 )	94.4 ( 15.91 )	91.5 ( 14.45 )	93.5 ( 17 )	116.1 ( 23.26 )
Week 5, n=8, 16, 9, 16, 3, 8	79.3 ( 9.44 )	82.5 ( 13.87 )	95.3 ( 14.96 )	92.4 ( 15.18 )	89 ( 15.52 )	99.8 ( 19.51 )
Week 6, n=8, 16, 9, 17, 4, 9	77 ( 9.5 )	83.2 ( 11.01 )	86.8 ( 11.62 )	90.1 ( 17.74 )	84.8 ( 13.15 )	103 ( 23.14 )
Week 7, n=8, 16, 9, 17, 4, 9	74.1 ( 6.92 )	82.8 ( 11.68 )	96.7 ( 15.39 )	91.6 ( 17.68 )	101.5 ( 16.6 )	105.3 ( 15.18 )
MBP, n=8, 16, 9, 17, 4, 11	88.3 ( 7.72 )	97.6 ( 7.51 )	106.1 ( 11.92 )	108.6 ( 17.08 )	106.8 ( 12.28 )	117.5 ( 21.68 )

Notes
[119] - Safety Population
[120] - Safety Population
[121] - Safety Population
[122] - Safety Population
[123] - Safety Population
[124] - Safety Population

No statistical analyses for this end point

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3

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End point title

Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3

End point 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. 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.

End point type

Secondary

End point timeframe

From Week 1 to Follow-up Week 4 of Part 2/3, up to Study Week 35

End point values	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
Number of subjects analysed	24 ^[125]	26 ^[126]	15 ^[127]
Units: Beats per minute
arithmetic mean (standard deviation)
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 ( 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 )	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 ( 10.2 )	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 ( 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 ( 8.72 )
Week 16, n=17, 14, 8	81.3 ( 11.24 )	91.4 ( 15.08 )	99.8 ( 17.16 )
Week 17, n=13, 11, 5	79.7 ( 11.69 )	96.1 ( 20.8 )	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 ( 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 ( 5.5 )	98.6 ( 18.2 )
Week 23, n=8, 7, 6	80.4 ( 11.25 )	89 ( 22.38 )	96.2 ( 10.68 )
Week 24, n=23, 23, 11	81.2 ( 9.7 )	93.5 ( 12.59 )	95.3 ( 17.75 )
FU Week 1, n=6, 6, 3	86.3 ( 5.85 )	94.2 ( 18.03 )	100 ( 20.07 )
FU Week 2, n=8, 7, 7	83 ( 8.54 )	87.9 ( 12.77 )	110 ( 27.47 )
FU Week 3, n=6, 5, 4	83.7 ( 13.03 )	92.4 ( 11.55 )	92 ( 12.19 )
FU Week 4, n=11, 13, 7	81.6 ( 11.89 )	92.3 ( 16.1 )	102.3 ( 18.87 )
MPB, n=24, 26, 15	102.2 ( 9.35 )	110.9 ( 15.03 )	121.2 ( 20.42 )

Notes
[125] - Safety Population.
[126] - Safety Population.
[127] - Safety Population.

No statistical analyses for this end point

Secondary: Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1

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End point title

Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1

End point 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, normal result, Neg, and range of pH (from 5-9 in increments of 0.5). Data was reported at BL(measurement from Day 1) and Week 24 (W24). Only those par available at the specified time points were analyzed(represented by n=X in the category titles). Different par may have been analyzed at different time points, so the number of par analyzed reflects everyone in the Safety Population.

End point type

Secondary

End point timeframe

Baseline (BL) and Week 24 of Part 1

End point values	Part 1 (Dose-Finding Period)
Number of subjects analysed	15 ^[128]
Units: Participants
number (not applicable)
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

Notes
[128] - Safety Population, only par from Part 1 and available at specified time points were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline (BL) and Week 7 During the Randomized Period, Part 2

Top of page

End point title

Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline (BL) and Week 7 During the Randomized Period, Part 2

End point 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, normal result, Neg, and range of pH(from 5-9 in increments of 0.5). Data was reported at BL (value from Day 1) and Week 7(W7). Only par available at the specified time points were analyzed(represented by n=X,X in the category titles). Different par may have been analyzed at different time points, so the number of par analyzed reflects everyone in the Safety Population.

End point type

Secondary

End point timeframe

Baseline and Week 7 of Part 2

End point values	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag
Number of subjects analysed	21 ^[129]	44 ^[130]
Units: Participants
number (not applicable)
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

Notes
[129] - Safety Population, only par in Part 2 and available at specified time points were analyzed.
[130] - Safety Population, only par in Part 2 and available at specified time points were analyzed.

No statistical analyses for this end point

Secondary: 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

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End point 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

End point 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, normal result, Neg, and range of pH(from 5-9 in increments of 0.5). Data was reported at BL (value from Day 1) and Week 24(W24). Only par available at the specified time points were analyzed(represented by n=X,X in the category titles). Different par may have been analyzed at different time points, so the number of par analyzed reflects everyone in the Safety Population.

End point type

Secondary

End point timeframe

Baseline and Week 24 of Part 2/3 up to Study Week 31

End point values	Part 2/3 (Eltrombopag Open-Label Period)
Number of subjects analysed	44 ^[131]
Units: Participants
number (not applicable)
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

Notes
[131] - Safety Population, only par in Part 2/3 available at specified time points were analyzed.

No statistical analyses for this end point

Secondary: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1

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End point title

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1 ^[132]

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. Safety Population: all participants who received at least one dose of the investigational product during Part 1 were analyzed.

End point type

Secondary

End point timeframe

From Treatment + 1 day up to Week 24 of Part1

Notes
[132] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Adverse events are presented by Part 1, 2, or 2/3 as separate endpoints.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[133]	5 ^[134]	5 ^[135]
Units: Participants
number (not applicable)
Any AE	5	5	5
Any SAE	1	1	0

Notes
[133] - Safety Population
[134] - Safety Population
[135] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2

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End point title

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2 ^[136]

End point description

End point type

Secondary

End point timeframe

From Treatment + 1 day up to Week 7 of Part 2

Notes
[136] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Adverse events are presented by Part 1, 2, or 2/3 as separate endpoints.

End point values	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
Number of subjects analysed	8 ^[137]	16 ^[138]	9 ^[139]	17 ^[140]	4 ^[141]	11 ^[142]
Units: Participants
number (not applicable)
Any AE	8	13	9	14	3	9
Any SAE	1	1	1	3	0	0

Notes
[137] - Safety Population
[138] - Safety Population
[139] - Safety Population
[140] - Safety Population
[141] - Safety Population
[142] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2/3

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End point title

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2/3

End point description

End point type

Secondary

End point timeframe

From Treatment + 1 day up to Week 31 of Part 2/3

End point values	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
Number of subjects analysed	24 ^[143]	26 ^[144]	15 ^[145]
Units: Participants
number (not applicable)
Any AE	22	26	14
Any SAE	3	5	0

Notes
[143] - Safety Population
[144] - Safety Population
[145] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts During Part 1

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End point title

Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts During Part 1 ^[146]

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 a change in visual acuity and worsening visual acuity due to cataracts since Baseline are presented for Part 1 Follow-up Visits at 3-months (FU3) and at 6-months (FU6). Change in visual acuity since Baseline is displayed under the left eye but applies to both eyes. Change in visual acuity (VA) is categorized as "yes" or "no". Change due to cataracts is categorized as "yes" or "no". Safety Population: all subjects who have received at least one dose of the investigational product during Part 1 were analyzed.

End point type

Secondary

End point timeframe

Baseline, 3 and 6-mo Follow-up of Part 1

Notes
[146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only represents the number of participants from Part 1.

End point values	Part 1 (Dose-Finding Period) Cohort 1	Part 1 (Dose-Finding Period) Cohort 2	Part 1 (Dose-Finding Period) Cohort 3
Number of subjects analysed	5 ^[147]	5 ^[148]	5 ^[149]
Units: Participants
number (not applicable)
Change in VA at FU3, no	1	1	2
Change in VA at FU3, yes	0	0	1
Change in VA at FU6, no	4	4	5
Change in VA at FU6, yes	0	0	0
Change due to cataracts at FU3, no	0	0	1
Change due to cataracts at FU3, yes	0	0	0
Change due to cataracts at FU6, no	0	0	0
Change due to cataracts at FU6, yes	0	0	0

Notes
[147] - Safety Population
[148] - Safety Population
[149] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts during Part 2/3

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End point title

Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts during Part 2/3

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. Number of participants with a change in visual acuity and change in visual acuity due to the worsening of cataracts since Baseline are presented for Part 2/3 Follow-up Visits at 3-months (FU3) and 6-months (FU6). Change in visual acuity since Baseline is displayed under the left eye but applies to both eyes. Change in visual acuity (VA) is categorized as "yes" or "no". Change due to cataracts is categorized as "yes" or "no". All participants who have received at least one dose of the investigational product during Part 2/3 were analyzed

End point type

Secondary

End point timeframe

Baseline (BL), 3 and 6 month (no) Follow-up (FU) of Part 2/3

End point values	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
Number of subjects analysed	24 ^[150]	26 ^[151]	15 ^[152]
Units: Participants
number (not applicable)
Change in VA at FU3, no	13	17	9
Change in VA at FU3, yes	4	1	2
Change in VA at FU6, no	16	22	6
Change in VA at FU6, yes	4	2	3
Change due to cataracts at FU3, no	4	1	2
Change due to cataracts at FU3, yes	0	0	0
Change due to cataracts at FU6, no	4	2	3
Change due to cataracts at FU6, yes	0	0	0

Notes
[150] - Safety Population
[151] - Safety Population
[152] - Safety Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On-treatment adverse events (AEs) and serious adverse events (SAEs) are defined as events occuring from the start of the investigational product plus one day until the end of treatment (up to Study Week 31)

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 (Dose-Finding Period)

Reporting 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.

Reporting group title

Part 2 (Randomized Period) -Placebo

Reporting 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 matching placebo for 7 weeks.

Reporting group title

Part 2 (Randomized Period) -Eltrombopag

Reporting group description

Reporting group title

Part 2/ 3 (Eltrombopag Open-Label Period)

Reporting 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. Par who received placebo during the Randomized Period followed the starting doses for each age Cohort specified for Part 2.

Serious adverse events	Part 1 (Dose-Finding Period)	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag	Part 2/ 3 (Eltrombopag Open-Label Period)
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 15 (13.33%)	2 / 21 (9.52%)	4 / 44 (9.09%)	8 / 65 (12.31%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	1 / 44 (2.27%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	1 / 44 (2.27%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	1 / 44 (2.27%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	1 / 44 (2.27%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Conjunctivitis
subjects affected / exposed	0 / 15 (0.00%)	1 / 21 (4.76%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lenticular opacities
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vitreous opacities
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Epistaxsis
subjects affected / exposed	1 / 15 (6.67%)	1 / 21 (4.76%)	0 / 44 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Impetigo
subjects affected / exposed	0 / 15 (0.00%)	1 / 21 (4.76%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	1 / 44 (2.27%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	0 / 15 (0.00%)	1 / 21 (4.76%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Part 1 (Dose-Finding Period)	Part 2 (Randomized Period) -Placebo	Part 2 (Randomized Period) -Eltrombopag	Part 2/ 3 (Eltrombopag Open-Label Period)
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 15 (100.00%)	17 / 21 (80.95%)	30 / 44 (68.18%)	59 / 65 (90.77%)
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Pyrexia
subjects affected / exposed	0 / 15 (0.00%)	3 / 21 (14.29%)	6 / 44 (13.64%)	15 / 65 (23.08%)
occurrences all number	0	3	6	18
Fatigue
subjects affected / exposed	0 / 15 (0.00%)	2 / 21 (9.52%)	3 / 44 (6.82%)	8 / 65 (12.31%)
occurrences all number	0	2	3	10
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	4 / 65 (6.15%)
occurrences all number	0	0	0	4
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	4 / 65 (6.15%)
occurrences all number	1	0	0	8
Menorrhagia
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	3 / 15 (20.00%)	3 / 21 (14.29%)	1 / 44 (2.27%)	11 / 65 (16.92%)
occurrences all number	5	6	2	27
Cough
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	3 / 44 (6.82%)	9 / 65 (13.85%)
occurrences all number	1	0	3	14
Oropharyngeal pain
subjects affected / exposed	1 / 15 (6.67%)	1 / 21 (4.76%)	5 / 44 (11.36%)	9 / 65 (13.85%)
occurrences all number	1	1	6	13
Sneezing
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Nasal congestion
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	5 / 65 (7.69%)
occurrences all number	0	0	0	5
Psychiatric disorders
Middle insomnia
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Investigations
Blood glucose decreased
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Weight increased
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Fall
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Injury
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	2	0	0	0
Laceration
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Excoriation
subjects affected / exposed	0 / 15 (0.00%)	2 / 21 (9.52%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	0	2	0	0
Nervous system disorders
Headache
subjects affected / exposed	8 / 15 (53.33%)	9 / 21 (42.86%)	13 / 44 (29.55%)	28 / 65 (43.08%)
occurrences all number	18	13	25	70
Paraesthesia
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Dizziness
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	5 / 65 (7.69%)
occurrences all number	0	0	0	5
Blood and lymphatic system disorders
Thrombocytosis
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	5 / 65 (7.69%)
occurrences all number	0	0	0	6
Eye disorders
Astigmatism
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	6 / 15 (40.00%)	6 / 21 (28.57%)	3 / 44 (6.82%)	10 / 65 (15.38%)
occurrences all number	11	9	3	12
Diarrhoea
subjects affected / exposed	5 / 15 (33.33%)	1 / 21 (4.76%)	7 / 44 (15.91%)	17 / 65 (26.15%)
occurrences all number	6	1	8	21
Abdominal pain
subjects affected / exposed	2 / 15 (13.33%)	2 / 21 (9.52%)	3 / 44 (6.82%)	15 / 65 (23.08%)
occurrences all number	3	2	4	18
Abdominal pain upper
subjects affected / exposed	2 / 15 (13.33%)	0 / 21 (0.00%)	0 / 44 (0.00%)	6 / 65 (9.23%)
occurrences all number	2	0	0	7
Toothache
subjects affected / exposed	2 / 15 (13.33%)	0 / 21 (0.00%)	3 / 44 (6.82%)	4 / 65 (6.15%)
occurrences all number	2	0	3	4
Gingival bleeding
subjects affected / exposed	1 / 15 (6.67%)	2 / 21 (9.52%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	2	0	0
Haematochezia
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Nausea
subjects affected / exposed	1 / 15 (6.67%)	4 / 21 (19.05%)	6 / 44 (13.64%)	15 / 65 (23.08%)
occurrences all number	1	5	9	34
Stomatitis
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Constipation
subjects affected / exposed	0 / 15 (0.00%)	0 / 21 (0.00%)	0 / 44 (0.00%)	6 / 65 (9.23%)
occurrences all number	0	0	0	6
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Pruritus
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Rash
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	5 / 65 (7.69%)
occurrences all number	1	0	0	6
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	1 / 15 (6.67%)	2 / 21 (9.52%)	1 / 44 (2.27%)	6 / 65 (9.23%)
occurrences all number	1	2	1	8
Arthralgia
subjects affected / exposed	0 / 15 (0.00%)	2 / 21 (9.52%)	2 / 44 (4.55%)	6 / 65 (9.23%)
occurrences all number	0	2	3	9
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	5 / 15 (33.33%)	2 / 21 (9.52%)	11 / 44 (25.00%)	24 / 65 (36.92%)
occurrences all number	6	2	12	35
Nasopharyngitis
subjects affected / exposed	2 / 15 (13.33%)	0 / 21 (0.00%)	0 / 44 (0.00%)	8 / 65 (12.31%)
occurrences all number	4	0	0	10
Viral upper respiratory tract infection
subjects affected / exposed	2 / 15 (13.33%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	2	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Lower respiratory tract infection
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Molluscum contagiosum
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Otitis media
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Respiratory tract infection
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Skin infection
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Tonsillitis
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0
Viral pharyngitis
subjects affected / exposed	1 / 15 (6.67%)	0 / 21 (0.00%)	0 / 44 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	0	0

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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

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 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)

Primary: 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)

Secondary: 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)

Secondary: 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)

Secondary: Weighted Mean Platelet Count

Secondary: Weighted Mean Platelet Count

Secondary: Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1

Secondary: Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1

Secondary: Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/3

Secondary: Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/3

Secondary: Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3

Secondary: Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3

Secondary: 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

Secondary: 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

Secondary: Maximum Duration for Which a Participant (par) Continuously Maintained a Platelet Count of >=50 Gi/L During the 24 Weeks of Eltrombopag Treatment (trt) in Part 2/3

Secondary: Maximum Duration for Which a Participant (par) Continuously Maintained a Platelet Count of >=50 Gi/L During the 24 Weeks of Eltrombopag Treatment (trt) in Part 2/3

Secondary: Percentage of Participants Who Reduced or Discontinued Baseline Concomitant Idiopathic Thrombocytopenic Purpura(ITP) Medications During the 24 Weeks of Eltrombopag Treatment During Part 1

Secondary: Percentage of Participants Who Reduced or Discontinued Baseline Concomitant Idiopathic Thrombocytopenic Purpura(ITP) Medications During the 24 Weeks of Eltrombopag Treatment During Part 1

Secondary: Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/3

Secondary: Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/3

Secondary: Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3

Secondary: Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3

Secondary: 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

Secondary: 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

Secondary: Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2

Secondary: Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: 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

Secondary: Number of Participants With the Indicated Clinical Chemistry Parameter Falling Outside of the Reference Range (RR) Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

Secondary: Number of Participants With the Indicated Clinical Chemistry Parameter Falling Outside of the Reference Range (RR) Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

Secondary: Number of Participants (par) With the Indicated Hematology Parameters Falling Outside of the Reference Range (RR) at Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

Secondary: Number of Participants (par) With the Indicated Hematology Parameters Falling Outside of the Reference Range (RR) at Any Time Post-Baseline During Part 1, Part 2, and Part 2/3

Secondary: 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

Secondary: 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

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3

Secondary: Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3

Secondary: Number of Participants (par) With the Indicated Vital Signs Falling Outside of the Reference Range (RR) During Part 1, Part 2, and Part 2/3

Secondary: Number of Participants (par) With the Indicated Vital Signs Falling Outside of the Reference Range (RR) During Part 1, Part 2, and Part 2/3

Secondary: Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1

Secondary: Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1

Secondary: Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2

Secondary: Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2

Secondary: Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3

Secondary: Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3

Secondary: Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3

Secondary: Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1

Secondary: Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1

Secondary: Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline (BL) and Week 7 During the Randomized Period, Part 2

Secondary: Number of Participants (par) for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline (BL) and Week 7 During the Randomized Period, Part 2

Secondary: 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

Secondary: 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

Secondary: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1