Trial Outcomes & Findings for EXTEND (Eltrombopag Extended Dosing Study) (NCT NCT00351468)

NCT ID: NCT00351468

Last Updated: 2017-04-17

Results Overview

All safety evaluation findings considered to be adverse events are reported in the Adverse Event section.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

302 participants

Primary outcome timeframe

Start date was the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product up to week 364

Results posted on

2017-04-17

Participant Flow

Subjects were previously enrolled in a study of eltrombopag: TRA100773A, TRA100773B, TRA102537/RAISE, or TRA108057/REPEAT. Eligibility of consenting subjects was assessed during the screening period of up to 28 days prior to Day 1 of treatment.

Participant milestones

Participant milestones
Measure	Eltrombopag Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Overall Study STARTED	302
Overall Study Subjects From TRA100773A	51
Overall Study Subjects From TRA100773B	61
Overall Study Subjects From TRA102537 Raise	146
Overall Study Subjects From TRA108057 Repeat	43
Overall Study Unknown - Not From Previous Trial	1
Overall Study COMPLETED	135
Overall Study NOT COMPLETED	167

Reasons for withdrawal

Reasons for withdrawal
Measure	Eltrombopag Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Overall Study Adverse Event	42
Overall Study Withdrawal by Subject	39
Overall Study Various -follow up w clinical team	39
Overall Study Lack of Efficacy	32
Overall Study Non-compliance	8
Overall Study Lost to Follow-up	4
Overall Study Protocol Violation	3

Baseline Characteristics

EXTEND (Eltrombopag Extended Dosing Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Age, Continuous	48.9 Years STANDARD_DEVIATION 15.61 • n=5 Participants
Sex: Female, Male Female	201 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants
Concomitant ITP Medication at Baseline Yes	101 Participant n=5 Participants
Concomitant ITP Medication at Baseline No	201 Participant n=5 Participants
Splenectomy Status at Baseline Yes	115 Participants n=5 Participants
Splenectomy Status at Baseline No	187 Participants n=5 Participants
Baseline Platelet Count <30 Gi/L	211 Participants n=5 Participants
Baseline Platelet Count 30 - 50 Gi/L	52 Participants n=5 Participants
Baseline Platelet Count > 50 Gi/L	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: Start date was the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product up to week 364

All safety evaluation findings considered to be adverse events are reported in the Adverse Event section.

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Overall Summary of On-Therapy Adverse Events (Safety Population) Any adverse event	277 Participants
Overall Summary of On-Therapy Adverse Events (Safety Population) Any serious adverse event	96 Participants
Overall Summary of On-Therapy Adverse Events (Safety Population) Adverse events related to study medication	133 Participants
Overall Summary of On-Therapy Adverse Events (Safety Population) Adverse events leading to withdrawal	41 Participants
Overall Summary of On-Therapy Adverse Events (Safety Population) Serious adverse events leading withdrawal	28 Participants

SECONDARY outcome

Timeframe: Baseline up to 2 years

Population: ITT population

Subjects who achieved maximum platelet count at least once during treatment. All platelet counts after an on-study splenectomy are not classed as responses. Platelet counts within 7 days after a platelet transfusion are not classed as responses. Platelet counts while taking an increased ITP medication or within 6 weeks after the end of an increased ITP medication are not classed as responses.

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication Baseline Platelet counts >= 30 Gi/L,	91 Participants
Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication Baseline Platelet counts >= 50 Gi/L,	42 Participants
Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication Maximum Platelet Count >= 30 Gi/L	276 Participants
Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication Maximum Platelet Count >= 50 Gi/L	259 Participants

SECONDARY outcome

Timeframe: Baseline up to Year 7/Week 364

Population: ITT population

If a subject has more than 1 platelet count result within a week, the lowest value observed is used to determine response. All platelet counts after an on-study splenectomy are not classed as responses. Platelet counts within 7 days after a platelet transfusion are not classed as responses. Platelet counts while taking an increased ITP medication or within 6 weeks after the end of an increased ITP medication are not classed as responses.

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Baseline Platelet counts >= 30 Gi/L, n=302	91 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Baseline Platelet counts >= 50 Gi/L, n=302	42 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 1 Platelet Count >= 30 Gi/L n=293	172 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 1 Platelet Count >= 50 Gi/L n=293	127 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 2 Platelet Count >= 30 Gi/L n=288	199 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 2 Platelet Count >= 50 Gi/L n=288	165 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 3 Platelet Count >= 30 Gi/L n=275	192 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 3 Platelet Count >= 50 Gi/L n=275	159 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 4 Platelet Count >= 30 Gi/L n=275	192 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 4 Platelet Count >= 50 Gi/L n=275	149 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 5 Platelet Count >= 30 Gi/L n=274	197 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 5 Platelet Count >= 50 Gi/L n=274	159 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 6 Platelet Count >= 30 Gi/L n=276	203 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 6 Platelet Count >= 50 Gi/L n=276	169 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 12 Platelet Count >= 30 Gi/L n=197	147 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Week 12 Platelet Count >= 50 Gi/L n=197	120 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Month 6/Week 26 Platelet Count >= 30 Gi/L n=130	93 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Month 6/Week 26 Platelet Count >= 50 Gi/L n=130	82 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 1/Week 52 Platelet Count >= 30 Gi/L n=83	62 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 1/Week 52 Platelet Count >= 50 Gi/L n=83	50 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 1.5/Week 78 Platelet Count >= 30 Gi/L n=63	47 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 1.5/Week78 Platelet Count >= 50 Gi/L n=63	41 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 2/Week 104 Platelet Count >= 30 Gi/L n=59	46 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 2/Week 104 Platelet Count >= 50 Gi/L n=59	42 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 2.5/Week 130 Platelet Count >= 30 Gi/L n=42	32 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 2.5/Week 130 Platelet Count >= 50 Gi/L n=42	28 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 3/Week 156 Platelet Count >= 30 Gi/L n=27	22 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 3/Week 156 Platelet Count >= 50 Gi/L n=27	19 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 3.5/Week 182 Platelet Count >= 30 Gi/L n=23	19 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 3.5/Week 182 Platelet Count >= 50 Gi/L n=23	17 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 4/Week 208 Platelet Count >= 30 Gi/L n=17	12 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 4/Week 208 Platelet Count >= 50 Gi/L n=17	11 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 4.5/Week 234 Platelet Count >= 30 Gi/L n=15	13 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 4.5/Week 234 Platelet Count >= 50 Gi/L n=15	12 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 5/Week 260 Platelet Count >= 30 Gi/L n=9	6 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 5/Week 260 Platelet Count >= 50 Gi/L n=9	6 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 5.5/Week 286 Platelet Count >= 30 Gi/L n=9	7 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 5.5/Week 286 Platelet Count >= 50 Gi/L n=9	7 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 6/Week 312 Platelet Count >= 30 Gi/L n=9	7 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 6/Week 312 Platelet Count >= 50 Gi/L n=9	7 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 6.5/Week 338 Platelet Count >= 30 Gi/L n=5	3 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 6.5/Week 338 Platelet Count >= 50 Gi/L n=5	3 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 7/Week 364 Platelet Count >= 30 Gi/L n=3	3 Participants
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication Year 7/Week 364 Platelet Count >= 50 Gi/L n=3	3 Participants

SECONDARY outcome

Timeframe: Baseline up to 2 years

Population: ITT

Responder in TRA100773: Platelet count 50 Gi/L and 2 x baseline (BL) at last on-treatment assessment. Responders in EXTEND: Platelet count 50 Gi/L and 2 x baseline (BL), 50 Gi/L, and 30 Gi/L at any time. Responder in RAISE: Platelet count 50GI/L and 2 x baseline at Week 6 assessment. Responders in EXTEND: Platelet count 50 Gi/L and 2 x baseline, 50 Gi/L, and 30 Gi/L at any time. Responder in REPEAT: Platelet count 50 GI/L and 2 x baseline (BL) at Week 6 assessment in Cycle 1. Responders in EXTEND: Platelet count 50 Gi/L and 2 x baseline (BL) 50 Gi/L, and 30 Gi/L at any time.

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL TRA100773 Responders >= 50 Gi/L in EXTEND, n=51	49 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL TRA100773 >=50 Gi/L and 2 x BL in EXTEND, n=51	47 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL TRA100773 Responders >= 30 Gi/L in EXTEND, n=51	49 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL RAISE Responders >= 50 Gi/L in EXTEND, n=59	54 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL RAISE >= 50 Gi/L and 2 x BL in EXTEND, n=59	53 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL RAISE Responders >= 30 Gi/L in EXTEND, n=51	55 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL REPEAT Responders >= 50 Gi/L in EXTEND, n=36	33 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL REPEAT>= 50 Gi/L and 2 x BL in EXTEND, n=36	33 Participants
Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL REPEAT Responders >= 30 Gi/L in EXTEND, n=36	35 Participants

SECONDARY outcome

Timeframe: Baseline up to 2 years

Sustain reduct: Sustained reduction 1 Denominator is number of subjects taking an ITP medication at baseline. 2 Denominator is number of subjects with a sustained reduction. Note: Sustained reduction defined as reduction from baseline in dose and/or frequency which is maintained for at least 4 weeks. Excludes sustained reductions started more than 1 day after last dose.

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL. ITP medication at baseline	101 Participants
Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL. Sustain reduct or stop at least 1 med [1] n=101	71 Participants
Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL. Permanently stopping at least 1 ITP med [1] n=101	53 Participants
Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL. Sustained reduction[1] n=101	70 Participants
Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL. Maximum sustained reduction ≥ 24 weeks[2] n=70	66 Participants

SECONDARY outcome

Timeframe: Baseline up to 2 years

Rescue treatment is defined as a composite of: new ITP medication, increased dose of a concomitant ITP medication, platelet transfusion, and splenectomy. Subjects may have received more than 1 type of rescue therapy

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag. New ITP medication, n=103	82 Participants
Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag. Increase in dose of ITP med from baseline, n=103	27 Participants
Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag. Platelet transfusion, n=103	21 Participants
Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag. Splenectomy, n=103	3 Participants

SECONDARY outcome

Timeframe: Baseline up to 2 years

The ITP bleeding score is a tool which has been designed specifically to assess the bruising and bleeding in patients with ITP across body sites, ranging from mild to severe. The WHO Grades were dichotomized into the following categories: - Grade 0, No bleeding -Grade 1 to 4, Any bleeding -Grade 0 to 1: No clinically significant bleeding -Grade 2 to 4 Clinically significant bleeding

Outcome measures

Outcome measures
Measure	Eltrombopag n=302 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Oral n=300 Grade 0	191 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Epistaxis n=300 Grade 0	204 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Epistaxis n=300 Grade 1	65 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Epistaxis n=300 Grade 2	31 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Gastrointestinal n=300 Grade 0	264 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Gastrointestinal n=300 Grade 1	26 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Gastrointestinal n=300 Grade 2	10 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Genitourinary n=300 Grade 0	262 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Genitourinary n=300 Grade 1	29 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Genitourinary n=300 Grade 2	9 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Gynecologic n=108 Grade 0	68 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Gynecologic n=108 Grade 1	15 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Gynecologic n=108 Grade 2	25 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Intracerebral hemorrhage n=300 Grade 0	297 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Intracerebral hemorrhage n=300 Grade 1	3 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Intracerebral hemorrhage n=300 Grade 2	0 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Ocular n=300 Grade 0	258 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Ocular n=300 Grade 1	37 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Ocular n=300 Grade 2	5 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Oral n=300 Grade 1	81 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Oral n=300 Grade 2	28 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Pulmonary n=300 Grade 0	287 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Pulmonary n=300 Grade 1	13 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Pulmonary n=300 Grade 2	0 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Skin, ecchymosis n=300 Grade 0	74 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Skin, ecchymosis n=300 Grade 1	159 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Skin, ecchymosis n=300 Grade 2	67 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Skin, petechiae n=300 Grade 0	142 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Skin, petechiae n=300 Grade 1	126 Participants
Maximum ITP Bleeding Score at Any Time During the Study During All Stages. Skin, petechiae n=300 Grade 2	32 Participants

SECONDARY outcome

Timeframe: Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years

The SF-36v2 assessment tool was used to obtain information about subjects' general health status and health-related quality of life. Until a formal assessment of minimal clinically important differences (MCID) is performed, changes from baseline of more than 0.5 standard deviations are suggested as clinically meaningful. Scores were transformed to a 0-100 point scale, with higher scores representing more positive answers. Scores were normalized to have a mean of 50 and SD of 10 to allow for comparison with outcomes from other chronic diseases. Recall period is the past week prior to administration. The change in scores was measured at the transitioning period and immediately prior to withdrawal/completion over 2 years, and the mean of these measurements was recorded to calculate the change from baseline and the best post baseline change score was reported for the entire group

Outcome measures

Outcome measures
Measure	Eltrombopag n=290 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Physical function (n=273	12.0 Points on a scale Interval 9.6 to 14.5
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Physical role (n=273)	14.2 Points on a scale Interval 11.5 to 16.9
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Bodily pain (n=273)	14.5 Points on a scale Interval 11.6 to 17.4
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 General health (n=273)	11.1 Points on a scale Interval 9.0 to 13.1
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Vitality (n=290)	13.9 Points on a scale Interval 11.6 to 16.3
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Social function (n=290)	12.6 Points on a scale Interval 10.2 to 15.1
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Emotional role (n=290)	11.4 Points on a scale Interval 8.7 to 14.0
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Mental health (n=290)	11.3 Points on a scale Interval 9.4 to 13.3
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Physical component summary (n=273)	5.3 Points on a scale Interval 4.5 to 6.2
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline SF-36v2 Mental component summary (n=290)	5.8 Points on a scale Interval 4.6 to 6.9

SECONDARY outcome

Timeframe: Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years

The MEI-SF (18 questions) was used to measure the reductions in mental energy, physical energy, and social motivation, either as symptoms of chronic ITP or as a side effect of pharmacotherapy. Minimal clinically important differences are estimated as 0.5 standard deviations or 7.5 points. All items use either a 7-level (0 to 6) or 5-level (0 to 4) response scale; items with a 5-level response scale were rescaled to 7-levels, and items were reverse-scored as necessary such that higher scores represent higher HRQoL Total score ranges from 0 to 108 points. Recall period is past week prior to administration. The change in scores was measured at the transitioning period and immediately prior to withdrawal/completion over 2 years, and the mean of these measurements was recorded to calculate the change from baseline and the best post baseline change score was reported for the entire group

Outcome measures

Outcome measures
Measure	Eltrombopag n=292 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Best Post-Baseline Change in the Short Form of the Motivation and Energy Scale (MEI-SF) From Any Time Point Compared With Baseline	11.3 Points on a scale Interval 9.1 to 13.5

SECONDARY outcome

Timeframe: Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years

Population: ITT

The FACIT-Fatigue consists of 13 questions in which patients rate the frequency (0-4) of symptoms of fatigue, in terms of tiredness, weakness, and fatigue Items were reverse-scored as necessary such that higher scores represent higher HRQoL Total score ranges from 0 to 52.Using anchor-based estimates, the minimally important difference in this subscale is 3.0 points. Recall period is past week prior to administration. The change in scores was measured at the transitioning period and immediately prior to withdrawal/completion over 2 years, and the mean of these measurements was recorded to calculate the change from baseline and the best post baseline change score was reported for the entire group

Outcome measures

Outcome measures
Measure	Eltrombopag n=291 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Best Post-Baseline Change in the FACIT-Fatigue 13 Item Subscale Score From Any Time Point Compared to Baseline	6.9 Points on a scale Interval 5.7 to 8.1

SECONDARY outcome

Timeframe: Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years

The FACT-TH6 consists of 6 questions in which patients rate (0-4) their general degree of worry related to bleeding and bruising, and resulting activity impairment and frustration. Although the six items do not constitute a formal domain or subscale of the FACT-Th assessment tool, these items had been identified by focus groups of patients with chronic ITP as important indicators of their HRQoL. Items were reverse-scored as necessary such that higher scores represent higher HRQoL. Total scores ranged from 0 to 24. Recall period is not specified. The change in scores was measured at the transitioning period and immediately prior to withdrawal/completion over 2 years, and the mean of these measurements was recorded to calculate the change from baseline and the best post baseline change score was reported for the entire group

Outcome measures

Outcome measures
Measure	Eltrombopag n=288 Participants Open-label eltrombopag was supplied in 25, 50, 75 mg tablets. All subjects started at 50mg once daily and dose was increased or decreased based on platelet count (target range 50-200Gi/L). Alternate days and interruption of dosing was permitted to maintain target range of platelet count. Doses could range from 25 to 75mg. Subjects could remain on treatment up to 2 years.
Best Post-Baseline Change in the FACT-TH6 at Any Time Point Compared to Baseline	4.0 Points on a scale Interval 3.4 to 4.6

Adverse Events

Eltrombopag, Treatment + 1 Day

Serious events: 96 serious events

Other events: 253 other events

Deaths: 0 deaths

Eltrombopag, >1 to 30 Days Post-Therapy

Serious events: 10 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Eltrombopag, Treatment + 1 Day n=302 participants at risk Eltrombopag, Treatment + 1 day	Eltrombopag, >1 to 30 Days Post-Therapy n=302 participants at risk Eltrombopag, \>1 to 30 Days Post-Therapy
Blood and lymphatic system disorders Anaemia	8.6% 26/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Gastrointestinal disorders Abdominal pain	6.0% 18/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Gastrointestinal disorders Abdominal pain upper	6.0% 18/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Gastrointestinal disorders Constipation	8.6% 26/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Gastrointestinal disorders Diarrhoea	15.2% 46/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.99% 3/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Gastrointestinal disorders Nausea	11.3% 34/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Gastrointestinal disorders Vomiting	6.3% 19/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
General disorders Fatigue	16.6% 50/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	1.3% 4/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
General disorders Influenza like illness	8.3% 25/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
General disorders Pyrexia	8.9% 27/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Bronchitis	8.3% 25/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Cystitis	5.3% 16/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Influenza	9.6% 29/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Nasopharyngitis	24.5% 74/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Pharyngitis	7.0% 21/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Sinusitis	6.6% 20/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Upper respiratory tract infection	22.8% 69/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	1.7% 5/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Urinary tract infection	10.6% 32/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Infections and infestations Viral infection	7.6% 23/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Investigations Alanine aminotransferase increased	7.6% 23/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Investigations Aspartate aminotransferase increased	7.0% 21/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Musculoskeletal and connective tissue disorders Arthralgia	14.9% 45/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Musculoskeletal and connective tissue disorders Back pain	12.9% 39/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Musculoskeletal and connective tissue disorders Pain in extremity	9.3% 28/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Nervous system disorders Dizziness	8.6% 26/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Nervous system disorders Headache	28.5% 86/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.99% 3/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Psychiatric disorders Insomnia	8.9% 27/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Respiratory, thoracic and mediastinal disorders Cough	10.6% 32/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Respiratory, thoracic and mediastinal disorders Epistaxis	7.6% 23/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.66% 2/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.9% 27/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Skin and subcutaneous tissue disorders Pruritus	5.6% 17/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Skin and subcutaneous tissue disorders Rash	8.3% 25/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.00% 0/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product
Vascular disorders Hypertension	7.3% 22/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product	0.33% 1/302 • Treatment + 1 Day: start date was between the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product