Trial Outcomes & Findings for Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures (NCT NCT00678587)

Last Updated: 2018-10-12

Results Overview

A platelet transfusion was given if the platelet count was \<50 giga (10\^9) per liter (Gi/L) before the procedure. A platelet transfusion was not given if the platelet count was \>80 Gi/L (based on a primary endpoint of success). For participants with platelet counts between 50 Gi/L and 80 Gi/L, platelet transfusions were administered at the discretion of the investigator and the physician performing the elective invasive procedure.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

292 participants

Primary outcome timeframe

Prior to, during, and up to seven days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26

Results posted on

2018-10-12

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Matching placebo	Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Overall Study STARTED	147	145
Overall Study COMPLETED	127	127
Overall Study NOT COMPLETED	20	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo	Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Overall Study Adverse Event	3	3
Overall Study Lack of Efficacy	1	0
Overall Study Protocol Violation	2	1
Overall Study Study Closed/Terminated	1	0
Overall Study Lost to Follow-up	3	5
Overall Study Investigator Discretion	2	6
Overall Study Withdrew Consent	8	3

Baseline Characteristics

Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=147 Participants Matching placebo	Eltrombopag 75 mg n=145 Participants Eltrombopag 75 mg administered orally once daily	Total n=292 Participants Total of all reporting groups
Age, Continuous	53.5 Years STANDARD_DEVIATION 11.78 • n=5 Participants	51.6 Years STANDARD_DEVIATION 11.04 • n=7 Participants	52.5 Years STANDARD_DEVIATION 11.44 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	49 Participants n=7 Participants	104 Participants n=5 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	96 Participants n=7 Participants	188 Participants n=5 Participants
Race/Ethnicity, Customized White	93 participants n=5 Participants	85 participants n=7 Participants	178 participants n=5 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	33 participants n=5 Participants	41 participants n=7 Participants	74 participants n=5 Participants
Race/Ethnicity, Customized Japanese/East Asian/South East Asian Heritage	19 participants n=5 Participants	14 participants n=7 Participants	33 participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander and White	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Number of participants categorized into the indicated Child-Pugh (CP) Class Child-Pugh Class A	59 participants n=5 Participants	68 participants n=7 Participants	127 participants n=5 Participants
Number of participants categorized into the indicated Child-Pugh (CP) Class Child-Pugh Class B	64 participants n=5 Participants	57 participants n=7 Participants	121 participants n=5 Participants
Number of participants categorized into the indicated Child-Pugh (CP) Class Child-Pugh Class C	17 participants n=5 Participants	10 participants n=7 Participants	27 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score at Baseline	12 scores on a scale n=5 Participants	12 scores on a scale n=7 Participants	12 scores on a scale n=5 Participants

PRIMARY outcome

Timeframe: Prior to, during, and up to seven days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26

Population: Intent-to-Treat (ITT) Population: all participants who were randomized to treatment

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Matching placebo	Eltrombopag 75 mg n=145 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With Chronic Liver Disease and Thrombocytopenia (Platelets <50 Gi/L) Who do Not Require a Platelet Transfusion Prior to, During, and up to 7 Days Following Elective Invasive Procedures	28 participants	104 participants

SECONDARY outcome

Timeframe: Prior to, during, and up to 7 days following elective invasive procedures (Study Days 16-19); therefore, this covers a time period from Baseline to Day 26

Population: ITT Population

The WHO Bleeding Scale was used to assess bleeding during the study. The range of possible scores is 0 to 4. Grade 0 is no bleeding; Grade 1 is petechiae (small \[1-2 millimeter\] red or purple spot on the body, caused by a minor hemorrhage); Grade 2 is mild blood loss; Grade 3 is gross blood loss (requiring a transfusion; and Grade 4 is debilitating blood loss (retinal or cerebral associated with fatality).

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Matching placebo	Eltrombopag 75 mg n=145 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With a World Health Organization (WHO) Bleeding Score >=2 During and up to 7 Days Following Elective Invasive Procedures	34 participants	25 participants

SECONDARY outcome

Timeframe: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26

Population: ITT Population

Platelet transfusion use was documented at every visit throughout the study from screening until the 4-week (30-day) post-procedure follow-up visit or at the time of participant withdrawal from the study.

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Matching placebo	Eltrombopag 75 mg n=145 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With the Indicated Number of Platelet Transfusions Administered 0	30 participants	106 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered 1	93 participants	24 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered 2	3 participants	1 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered 3	2 participants	0 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered 4	3 participants	0 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered 5	0 participants	0 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered 6	1 participants	0 participants
Number of Participants With the Indicated Number of Platelet Transfusions Administered Died/withdrew prior to any platelet transfusions	15 participants	14 participants

SECONDARY outcome

Timeframe: Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 day follow-up; early withdrawal; and maximum post-baseline

Population: ITT Population. The number of participants analyzed decreases over time due to missing measurements and to participants dropping out of the study.

Procedure +7 = Days 23-26; +14 = Days 30-33; +21 = Days 37-40; +30 = Days 46-49. Early withdrawal can occur at any time. Maximum post-baseline refers to any time point listed above for which the maximum value was reached (therefore this time point is variable).

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Matching placebo	Eltrombopag 75 mg n=145 Participants Eltrombopag 75 mg administered orally once daily
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Screening, n=147, 145	40.0 Gi/L Interval 8.0 to 70.0	40.0 Gi/L Interval 3.0 to 55.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Day 1, n=145, 141	40.0 Gi/L Interval 8.0 to 222.0	40.0 Gi/L Interval 12.0 to 62.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Day 8, n=139, 134	41.0 Gi/L Interval 6.0 to 190.0	58.5 Gi/L Interval 20.0 to 337.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Day 15, n=132, 131	39.0 Gi/L Interval 6.0 to 200.0	103.0 Gi/L Interval 25.0 to 397.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Days 16-19, n=50, 49	41.5 Gi/L Interval 18.0 to 250.0	107.0 Gi/L Interval 30.0 to 406.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Procedure + 7 day follow-up, n=128, 125	44.0 Gi/L Interval 17.0 to 150.0	148 Gi/L Interval 30.0 to 493.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Procedure + 14 day follow-up, n=116, 125	47.5 Gi/L Interval 13.0 to 370.0	110 Gi/L Interval 18.0 to 805.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Procedure + 21 day follow-up, n=120, 117	44.5 Gi/L Interval 11.0 to 200.0	62.0 Gi/L Interval 15.0 to 967.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Procedure + 30 day follow-up, n=125, 127	40.0 Gi/L Interval 10.0 to 200.0	50.0 Gi/L Interval 14.0 to 999.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Early withdrawal, n=9, 8	40.0 Gi/L Interval 11.0 to 195.0	41.0 Gi/L Interval 32.0 to 140.0
Median Platelet Count at Screening; Days 1, 8, 15, 16-19; Procedure + 7, 14, 21, 30 Day Follow-up; Early Withdrawal; and Maximum Post-baseline Maximum post-baseline, n=144, 140	53.0 Gi/L Interval 16.0 to 370.0	152 Gi/L Interval 32.0 to 999.0

SECONDARY outcome

Timeframe: Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 day follow-up; and maximum post-baseline

Population: ITT Population. The number of participants analyzed decreases over time due to missing measurements and to participants dropping out of the study.

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Matching placebo	Eltrombopag 75 mg n=145 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 7 Day FU, >400 Gi/L, n=128, 126	0 participants	4 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 14 Day FU, <50 Gi/L, n=117, 125	63 participants	22 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 14 Day FU, >80-<=200 Gi/L, n=117, 125	11 participants	62 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 14 Day FU, >200-<=400 Gi/L, n=117, 125	2 participants	17 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 14 Day FU, >400 Gi/L, n=117, 125	0 participants	3 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 21 Day FU, >80-<=200 Gi/L, n=121, 117	10 participants	38 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 21 Day FU, >200-<=400 Gi/L, n=121, 117	0 participants	7 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 21 Day FU, >400 Gi/L, n=121, 117	0 participants	1 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Maximum Post-Baseline, <50 Gi/L, n=144, 140	60 participants	11 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Maximum Post-Baseline, >=50-<=80 Gi/L, n=144, 140	53 participants	23 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Maximum Post-Baseline, >80-<=200 Gi/L, n=144, 140	28 participants	62 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Maximum Post-Baseline, >200-<=400 Gi/L, n=144, 140	3 participants	37 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Maximum Post-Baseline, >400 Gi/L, n=144, 140	0 participants	7 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 14 Day FU, >=50-<=80 Gi/L, n=117, 125	40 participants	21 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 21 Day FU, <50 Gi/L, n=121, 117	80 participants	38 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 21 Day FU, >=50-<=80 Gi/L, n=121, 117	30 participants	33 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Screening, <50 Gi/L, n=147, 145	133 participants	136 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Screening, >=50-<=80 Gi/L, n=147, 145	14 participants	8 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Screening, >80-<=200 Gi/L, n=147, 145	0 participants	0 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Screening, >200-<=400 Gi/L, n=147, 145	0 participants	0 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Screening, >400 Gi/L, n=147, 145	0 participants	0 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 8, <50 Gi/L, n=139, 135	98 participants	48 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 8, >=50-<=80 Gi/L, n=139, 135	34 participants	50 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 8, >80-<=200 Gi/L, n=139, 135	7 participants	33 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 8, >200-<=400 Gi/L, n=139, 135	0 participants	3 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 8, >400 Gi/L, n=139, 135	0 participants	0 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 15, <50 Gi/L, n=132, 131	98 participants	14 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 15, >=50-<=80 Gi/L, n=132, 131	26 participants	31 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 15, >80-<=200 Gi/L, n=132, 131	8 participants	67 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 15, >200-<=400 Gi/L, n=132, 131	0 participants	19 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Day 15, >400 Gi/L, n=132, 131	0 participants	0 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 7 Day FU, <50 Gi/L, n=128, 126	78 participants	11 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 7 Day FU, >=50-<=80 Gi/L, n=128, 126	38 participants	20 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 7 Day FU, >80-<=200 Gi/L, n=128, 126	12 participants	60 participants
Number of Participants With the Indicated Platelet Count at Screening; Days 8 and 15; Procedure + 7, 14, 21, 30 Day Follow-up (FU); and Maximum Post-baseline Procedure + 7 Day FU, >200-<=400 Gi/L, n=128, 126	0 participants	30 participants

SECONDARY outcome

Timeframe: Screening to Procedure +30 day follow-up or early withdrawal

Population: Safety population: all randomized participants who received at least one dose of study medication

An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect or an ocular event of clinical concern. Medical or scientific judgement is exercised in deciding whether reporting is appropriate in other situations.

Outcome measures

Outcome measures
Measure	Placebo n=145 Participants Matching placebo	Eltrombopag 75 mg n=142 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category AEs during study	85 participants	79 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Drug-related AEs in >1 participant	15 participants	31 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Throboembolic AEs	2 participants	6 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Bleeding AEs	25 participants	19 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Hepatobiliary AEs	16 participants	24 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Renal AEs	4 participants	2 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Malignancy AEs	1 participants	1 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Death on study	2 participants	3 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category SAEs in >1 participant during study	17 participants	19 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Drug-related SAEs in >1 participant	4 participants	9 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Thrombocytopenia	1 participants	1 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Progression of pre-existing cataract n=145,143	2 participants	0 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Incident cataract develpment n=145,143	2 participants	4 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Decrease in visual acuity n=121,124	19 participants	21 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Renal function abnormality n=145,143	27 participants	28 participants
Number of Participants Experiencing an Adverse Event (AEs) and Serious Adverse Event (SAEs) Within the Indicated Category Clinically significant change in ECG n=128,130	0 participants	1 participants

SECONDARY outcome

Timeframe: Screening to Procedure +30 day follow-up or early withdrawal

Population: Safety Population

Outcome measures

Outcome measures
Measure	Placebo n=145 Participants Matching placebo	Eltrombopag 75 mg n=143 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With a Serious Adverse Event That Occurred in Greater Than One Participant	4 participants	9 participants

SECONDARY outcome

Timeframe: Screening or Baseline and at End of Study (Procedure +30 day follow-up or withdrawal visit)

Population: Safety Population: all randomized participants who received at least one dose of study medication. Data are missing for some participants.

The progression of pre-existing cataracts was measured by the use of slit lamp examination. Decrease in visual acuity is defined as the loss of 3 or more lines of visual acuity in either eye (0.3 log minimal angle of resolution \[logMAR\], 15 letters on the standard Early Treatment Diabetic Retinopathy Study chart).

Outcome measures

Outcome measures
Measure	Placebo n=145 Participants Matching placebo	Eltrombopag 75 mg n=143 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With the Indicated Event Relating to Vision Progression of pre-existing cataract, n=145, 143	2 participants	0 participants
Number of Participants With the Indicated Event Relating to Vision Cataract development, n=145, 143	2 participants	4 participants
Number of Participants With the Indicated Event Relating to Vision Decrease in visual acuity, n=121, 124	19 participants	21 participants

SECONDARY outcome

Timeframe: Screening to Procedure +30 day follow-up or early withdrawal

Population: Safety Population

Renal function abnormality was defined by threshold values for: serum creatinine: change from baseline of \>=0.3 and \<0.5 milligrams (mg)/deciliter (dL) (\>=26.6 and \<44.3 micromoles \[umol\]/L) or change from baseline of \>=0.5 mg/dL (\>=44.3 umol/L); microscopic urine analysis: cellular casts pathologic (as defined by local standards of microscopic urine analysis); urine protein/creatinine ratio (UP/CR): \>0.5 mg/mg; Glomerular Filtration Rate (GFR) as determined by the Cockcroft-Gault formula and urine dipstick test.

Outcome measures

Outcome measures
Measure	Placebo n=145 Participants Matching placebo	Eltrombopag 75 mg n=143 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With Renal Function Abnormality	27 participants	28 participants

SECONDARY outcome

Timeframe: Screening, Baseline, Day 15, and Withdrawal

Population: Safety Population. Data were missing for some participants.

A 12-lead ECG was obtained in duplicate at screening, baseline, Day 15, and withdrawal from the study. Participants rested supine for 5 minutes before the 12-lead ECG was recorded. A 30 second rhythm strip was obtained, and the ECG was calibrated, labelled, and initialled by the person performing the recording. A written, interpretive assessment detailing clinical significance was produced, dated, and signed off by the physician at the site.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Matching placebo	Eltrombopag 75 mg n=130 Participants Eltrombopag 75 mg administered orally once daily
Number of Participants With a Clinically Significant Change in Electrocardiogram (ECG) Results	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 14

Population: PK Subpopulation: all participants who were treated with eltrombopag and provided evaluable PK samples

AUC(0-tau) is the area under a concentration versus time curve between dose interval following repeat dosing. It is a measure of systemic drug exposure.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Matching placebo	Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Pharmacokinetics (PK) of Eltrombopag, Steady State AUC(0-tau)	250 hour*micrograms (ug)/milliliter (mL) Interval 211.0 to 296.0	—

SECONDARY outcome

Timeframe: Day 14

Population: PK Subpopulation

Cmax is the steady state peak plasma concentration of a drug observed after its administration.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Matching placebo	Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Pharmacokinetics (PK) of Eltrombopag, Cmax	11.6 ug/mL Interval 9.8 to 13.6	—

SECONDARY outcome

Timeframe: Day 14

Population: PK Subpopulation

t1/2 is the half life of a drug based on its terminal phase. Half life is defined as the time necessary to halve the plasma concentration.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Matching placebo	Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Pharmacokinetics (PK) of Eltrombopag, t1/2	70.3 hours Interval 60.7 to 81.5	—

SECONDARY outcome

Timeframe: Day 14

Population: PK Subpopulation

CL/F is the apparent plasma clearance, where CL is an estimate of the total body clearance, and F is the fraction of dose absorbed. Total clearance is the volume of blood cleared of the drug by the various elimination processes (metabolism and excretion) per unit time.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Matching placebo	Eltrombopag 75 mg Eltrombopag 75 mg administered orally once daily
Pharmacokinetics (PK) of Eltrombopag, CL/F	0.30 Liters/hour Interval 0.25 to 0.36	—

SECONDARY outcome

Timeframe: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26

Population: ITT Population. Data are missing for some participants.

The number of days spent in the hospital was analyzed as an indication of medical resource utilization throughout the study.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Matching placebo	Eltrombopag 75 mg n=144 Participants Eltrombopag 75 mg administered orally once daily
Mean Number of Days Spent in the Hospital	1.3 days Standard Deviation 3.77	1.7 days Standard Deviation 6.43

SECONDARY outcome

Timeframe: Prior to, during, and up to 4 weeks (30 days) following elective invasive procedures (Days 16-19); therefore, this covers a time period from Baseline to Day 26

Population: ITT Population. Data are missing for some participants.

The number of unscheduled events was analyzed as an indication of medical resource utilization throughout the study.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Matching placebo	Eltrombopag 75 mg n=144 Participants Eltrombopag 75 mg administered orally once daily
Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures Unscheduled office visits	0.8 unscheduled events Standard Deviation 1.64	1.0 unscheduled events Standard Deviation 2.91
Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures Unscheduled laboratory tests	1.1 unscheduled events Standard Deviation 3.78	1.8 unscheduled events Standard Deviation 5.67
Mean Number of Unscheduled Office Visits, Unscheduled Laboratory Tests, and Unscheduled Procedures Unscheduled procedures	0.3 unscheduled events Standard Deviation 0.81	0.4 unscheduled events Standard Deviation 1.65

Adverse Events

Placebo

Serious events: 17 serious events

Other events: 35 other events

Deaths: 0 deaths

Eltrombopag 75 mg

Serious events: 19 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=145 participants at risk Matching placebo	Eltrombopag 75 mg n=143 participants at risk Eltrombopag 75 mg administered orally once daily
Nervous system disorders Headache	4.1% 6/145 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.	7.7% 11/143 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.
General disorders Pyrexia	6.9% 10/145 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.	5.6% 8/143 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.
Gastrointestinal disorders Abdominal pain	4.8% 7/145 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.	4.9% 7/143 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.
Gastrointestinal disorders Nausea	4.8% 7/145 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.	4.9% 7/143 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.
Gastrointestinal disorders Diarrhoea	3.4% 5/145 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.	4.9% 7/143 • Adverse events (AEs) and serious adverse events (SAEs) with an onset on or after the start date of study medication were collected until the end of the study (up to the end of Week 7). The Safety Population, comprised of all randomized participants who received at least one dose of study medication, was used for the collection of AEs and SAEs.

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