Phase 2, Pharmacokinetics Study of Eltrombopag in Japanes... | NCT00861601

Label	Type	Description	Intervention Names
low dose	Experimental	eltrombopag 12.5 mg/day	Drug: eltrombopag 12.5 milligrams (mg) tablet
middle dose	Experimental	eltrombopag 25 mg/day	Drug: eltrombopag 25 mg tablet
high dose	Experimental	eltrombopag 37.5 mg/day	Drug: eltrombopag 12.5 milligrams (mg) tablet Drug: eltrombopag 25 mg tablet

Name	Type	Description	Arm Group Labels	Other Names
eltrombopag 12.5 milligrams (mg) tablet	Drug	eltrombopag 12.5 mg tablet once a day	high dose low dose

Measure	Description	Time Frame
Change From Baseline in Platelet Counts on Day 15	Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value.	Baseline, Day 15

Measure	Description	Time Frame
Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate)	Exploratory analysis was conducted to see a dose response/trend when a dose goes high with the changes from baseline in platelet counts (12.5 mg, 25 mg, and 37.5 mg) on Day 15 of each subject. The data were analyzed with baseline of platelet counts as covariate for the following dose response pattern using contrast: (1) linearity, (2) saturation at the medium dose, (3) onset of response at the high dose.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject who agree to comply with protocol requirements and instructions and who provide signed and dated written informed consent.
Male and female subjects, ≥20 years of age (at the time of informed consent) with chronic liver disease.
Child-Pugh score <=9.
A baseline platelet count <50,000/mcL.
A baseline serum sodium level >130 mEq/L.
Haemoglobin concentration >8 g/dL, stable for at least 4 weeks.
A female is eligible to enter and participate in the study if she is of:

Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:

Has had a hysterectomy
Has had a bilateral oophorectomy (ovariectomy)
Has had a bilateral tubal ligation
Is post-menopausal (demonstrate total cessation of menses for longer than one year)

Childbearing potential, has a negative urine and/or serum pregnancy test at screening, and within the 24 hour period prior to the first dose of investigational product and uses one of the following acceptable methods of contraception:

Complete abstinence from intercourse.
Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide).
Male partner who is sterile (diagnosed by a qualified medical professional) prior to the female subject's study entry and is the sole sexual partner for that female.
Oral contraceptive (combined).
Subject has no physical limitation to ingest and retain oral medication.

Exclusion Criteria:

Subjects with known or suspected hypersensitivity, intolerance or allergy to any of the ingredients in eltrombopag tablets.
Evidence of portal vein thrombosis on abdominal imaging (ultrasound with Doppler or appropriate magnetic resonance imaging/computed tomography (MRI/CT) imaging techniques) within 3 months before the start of the study.
History of arterial or venous thrombosis (including Budd-Chiari Syndrome),

AND ≥ two of the following risk factors:

hereditary thrombophilic disorders (e.g. antithrombinIII (ATIII) deficiency, etc.)
hormone replacement therapy
systemic contraception therapy (containing oestrogen)
smoking
diabetes
hypercholesterolemia
medication for hypertension or cancer
Human Immunodeficiency Virus (HIV) infection.
History of drug/alcohol abuse or dependence within 1 year prior to screening.
Any disease condition associated with current active World Health Organization (WHO) Grade 3 or 4 bleeding.
Active infection requiring systemic antibiotic therapy.
Pregnant, nursing mothers, women who may be pregnant, or women who plan to become pregnant during the time of study participation.
Treatment with platelet transfusion within 2 weeks prior to Day 1.
Treatment with interferon within 4 weeks prior to Day 1.
Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
History of platelet agglutination abnormality.
History of porphyria.
Subjects who are deemed unsuitable for the study by the investigator (or subinvestigator).

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Fukuoka		810-8563	Japan
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
22674141	Background	Kawaguchi T, Komori A, Seike M, Fujiyama S, Watanabe H, Tanaka M, Sakisaka S, Nakamuta M, Sasaki Y, Oketani M, Hattori T, Katsura K, Sata M. Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study. J Gastroenterol. 2012 Dec;47(12):1342-51. doi: 10.1007/s00535-012-0600-5. Epub 2012 Jun 8.

ID	Title	Description
FG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
FG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

ID	Title	Description
BG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
BG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
BG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00012 BG00114 BG00212 BG00338

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Platelet Counts on Day 15

Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value.

Full Analysis Set (FAS): all enrolled participants, excluding those who received no doses of eltrombopag during the treatment period, those without a baseline platelet assessment, and those without at least one on-therapy (scheduled or unscheduled) platelet assessment.

Posted

Mean

95% Confidence Interval

10^9/Liter

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Units	Counts
Participants	OG00012 OG00114 OG00212

Title

Denominators

Categories

Title	Measurements
	OG00024.8(8.2 to 41.4) OG00154.0(28.2 to 79.8) OG00260.0(29.3 to 90.7)

Secondary

Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline Platelet Counts as Covariate)

Exploratory analysis was conducted to see a dose response/trend when a dose goes high with the changes from baseline in platelet counts (12.5 mg, 25 mg, and 37.5 mg) on Day 15 of each subject. The data were analyzed with baseline of platelet counts as covariate for the following dose response pattern using contrast: (1) linearity, (2) saturation at the medium dose, (3) onset of response at the high dose.

FAS

Posted

Mean

95% Confidence Interval

10^9/Liter

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 mg of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Analysis of Covariance for Three Patterns of Dose Response Using the Change From Baseline in Platelet Counts (Baseline of Platelet Counts and Child-Pugh Class as Covariates)

Exploratory analysis was conducted to see a dose response/trend when a dose goes high with the changes from baseline in platelet counts (12.5 mg, 25 mg, and 37.5 mg) on Day 15 of each subject. The data were analyzed with baseline of platelet counts and Child-Pugh class as covariate for the following dose response pattern using contrast: (1) linearity, (2) saturation at the medium dose, (3) onset of response at the high dose.

FAS

Posted

Mean

95% Confidence Interval

10^9/Liter

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 mg of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Percent Change From Baseline in Platelet Counts on Day 15

Platelet counts were measured by blood draw. Change from Baseline was calculated as the Day 15 value minus the Baseline value.

FAS

Posted

Mean

95% Confidence Interval

Percent change

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Platelet Counts by Treatment Visit

Platelet counts were measured by blood draw. The Final Assessment Point is the last visit during the treatment period, which is Day 15 or Day 22.

FAS. The number of participants analyzed varies by visit, because the platelet count data on 4 days post-treatment in one participant in the 37.5 mg group are missing and the platelet count data post-specific therapies affecting the evaluation of efficacy are excluded from this efficacy analysis.

Posted

Median

Full Range

10^9/Liter

Day 1 (Baseline), Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Platelet Counts by Post-Treatment Visit

Platelet counts were measured by blood draw.

Posted

Median

Full Range

10^9/Liter

4 days post-treatment, 8 days post-treatment, and 15 days post-treatment

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Platelet Counts at Day 22

Platelet counts were measured by blood draw. The Final Assessment Point is the last visit during the treatment period, which is Day 15 or Day 22.

FAS. Participants in the 12.5 mg group have no data on Day 22 because they received the medication for only 14 days. Only 6 participants in the 25 mg group and 2 participants in the 37.5 mg group received the medication for an additional week, because they had a platelet count <80 x 10^9/Liter on Day 15.

Posted

Median

Full Range

10^9/Liter

Day 22

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Change From Baseline in Platelet Counts by Treatment Visit

Platelet counts were measured by blood draw. The Final Assessment Point is the last visit during the treatment period, which is Day 15 or Day 22. Change from Baseline was calculated as the value at each visit minus the Baseline value.

FAS. The number of participants analyzed varies by visit, because the platelet count data on 4 days post-treatment in one participant in the 37.5 mg group is missing and the platelet count data post-specific therapies affecting the evaluation of efficacy are excluded from this efficacy analysis.

Posted

Mean

Standard Deviation

10^9/Liter

Baseline, Day 8, Day 15, and Final Assessment Point (Day 15 or Day 22)

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Change From Baseline in Platelet Counts by Post-Treatment Visit

Platelet counts were measured by blood draw. Change from Baseline was calculated as the value at each visit minus the Baseline value.

Posted

Mean

Standard Deviation

10^9/Liter

4 days post-treatment, 8 days post-treatment, and 15 days post-treatment

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Percentage of Responders on Day 15

A responder was defined as a participant with a platelet count within the target range (>=80 x 10^9/Liter) on Day 15.

FAS

Posted

Mean

95% Confidence Interval

percentage of responders

Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Units

Secondary

Percentage of Responders on Day 22

A responder was defined as a participant with a platelet count within the target range (>=80 x 10^9/Liter) on Day 22 after receiving eltrombopag for an additional week from Day 15, on which his or her platelet count was <80 x 10^9/Liter.

Posted

Mean

95% Confidence Interval

percentage of responders

Day 22

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Change From Baseline in Platelet Counts on Day 15 by Child-Pugh Class

Change from Baseline was calculated as the Day 15 value minus the Baseline value. The Child-Pugh (CP) score (ranging from 5 to 15, with 5 being mild and 15 being severe), calculated based on total bilirubin, serum albumin, international normalized ratio, ascites, and hepatic encephalopathy, is used to assess the severity of liver disease. A CP score of 5 or 6 is classified as Class A (mild), a score of 7-9 is classified as Class B (moderate), and a score >=10 is classified as Class C (severe). Participants with a CP score <10 were enrolled in the study.

FAS. The number of participants categorized as Class A or Class B is given in the category titles.

Posted

Mean

Standard Deviation

10^9/Liter

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg

Secondary

Change From Baseline in Platelet Counts on Day 15 by Sex

Change from Baseline was calculated as the Day 15 value minus the Baseline value. The numbers of females and males in each treatment group are illustrated by the "n's" in the category titles.

FAS

Posted

Mean

Standard Deviation

10^9/Liter

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Change From Baseline in Platelet Counts on Day 15 by Age

Change from Baseline was calculated as the Day 15 value minus the Baseline value. The numbers of participants in each age category are illustrated by the "n's" in the category titles.

FAS

Posted

Mean

Standard Deviation

10^9/Liter

Baseline, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.
OG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.
OG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.

Secondary

Log-transformed Cmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg

PK Parameter Population: all participants from whom a PK sample was obtained and analyzed and whose PK parameter data was evaluated. One of the 12 participants took a prohibited medication that might have decreased the absorption of eltrombopag during the treatment period and was hence excluded from the PK Parameter Population.

Posted

Geometric Mean

95% Confidence Interval

nanograms/milliliter (ng/ml)

Day 14, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.

Units	Counts
Participants	OG000

Secondary

Log-transformed Tmax on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg

PK Parameter Population

Posted

Geometric Mean

95% Confidence Interval

hours

Day 14, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.

Units	Counts
Participants	OG000

Secondary

Log-transformed AUC(0-t) and AUC(0-24) on Days 14 and 15 in Participants Receiving Eltrombopag 12.5 mg

Serial PK samples were collected over a 24-hour (h) period on Days 14 and 15 in participants receiving eltrombopag 12.5 mg. A total of 8 blood samples (3 milliliters per sample) were collected at pre-dose, and at 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, and 24 h post-dose. AUC(0-t)=area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration, and AUC(0-24)=area under the concentration-time curve from 0 (pre-dose) to 24 hours.

PK Parameter Population

Posted

Geometric Mean

95% Confidence Interval

hours * ng/ml

Day 14, Day 15

ID	Title	Description
OG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0022 affected12 at risk
Ascites	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0011 affected14 at risk EG0021 affected12 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Nausea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Odynophagia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Vomiting	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0021 affected12 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Constipation	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Pyrexia	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0013 affected14 at risk EG0022 affected12 at risk
Malaise	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Chest pain	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Fatigue	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Oedema peripheral	General disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Postoperative fever	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0003 affected12 at risk EG0010 affected14 at risk EG0022 affected12 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0002 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Wound	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0024 affected12 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Alanine aminotransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0002 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0002 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
White blood cell count increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Blood bilirubin increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Blood pressure decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
C-reactive protein increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Eosinophil count increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Haematocrit decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Haemoglobin decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Lymphocyte count decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Neutrophil count decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Oxygen saturation decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Red blood cell count decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Urine output decreased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 affected12 at risk EG0010 affected14 at risk EG0022 affected12 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Renal impairment	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0021 affected12 at risk
Renal disorder	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Splenic vein thrombosis	Blood and lymphatic system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Blepharitis	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Eye pain	Eye disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Nasopharyngitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Urinary tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected12 at risk EG0010 affected14 at risk EG0021 affected12 at risk
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0011 affected14 at risk EG0020 affected12 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected12 at risk EG0010 affected14 at risk EG0020 affected12 at risk

ID	Term
D004304	Dosage Forms
D004364	Pharmaceutical Preparations

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Eltrombopag 12.5 mg	Participants received 12.5 milligrams (mg) of eltrombopag once daily for 14 days.	0	12	6	12
EG001	Eltrombopag 25 mg	Participants received 25 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.	0	14	7	14
EG002	Eltrombopag 37.5 mg	Participants received 37.5 mg of eltrombopag once daily for 14 days. Participants with a platelet count <80 x 10^9/Liter on Day 15 received eltrombopag for an additional week if the participant agreed to it and the investigator considered it appropriate.	1	12	9	12