A Safety and Efficacy Study of Eltrombopag in Subjects With AML

A Randomized, Blinded, Placebo-Controlled, Dose Finding Study to Assess the Safety and Efficacy of the Oral Thrombopoietin Receptor Agonist, Eltrombopag, Administered to Subjects With Acute Myelogenous Leukaemia (AML) Receiving Induction Chemotherapy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01890746

Enrollment

148

Registered

2013-07-02

Start date

2013-09-05

Completion date

2017-01-25

Last updated

2019-09-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Leukaemia

Keywords

AML, de novo AML, leukemia, sAML/MDS, acute myeloid leukemia, acute myelogenous leukemia (AML), secondary acute myeloid leukemia, ETB115, Eltrombopag, thrombocytopenia, oral thrombopoietin receptor agonist

Brief summary

The purpose of this randomized, blinded, placebo-controlled study was to provide clinical safety and exploratory efficacy data on the use of Eltrombopag in adult subjects with Acute Myeloid Leukemia (AML) receiving standard induction chemotherapy with daunorubicin plus cytarabine. A minimum of 120 evaluable subjects newly diagnosed with AML was stratified by antecedent malignant hematologic disorder and age.

Interventions

DRUGDaunorubicin

For subjects between the ages of 18 and 60 years, 90 mg/m2/day by bolus IV injection through a freshly established free-flowing IV line for 10-15 minutes on days 1, 2, and 3. For subjects \> 60 years: daunorubicin dose was adjusted to 60mg /m2.

DRUGCytarabine

100 mg/m2/day continuous IV infusion on Days 1 through 7.

DRUGEltrombopag

200 mg orally, once daily, beginning on Day 4 of the first cycle of induction. After 7 days, the dose of the Investigational Product (IP) was to be increased to 300 mg if platelet counts were \<100 Gi/L. IP continued until achievement of platelet count of at least 200 Gi/L or assessment of remission of bone marrow status or a maximum of 42 days after initiation of most recent induction. In subjects of East Asian heritage 100 mg orally once daily (a 50% dose reduction) was used and after 7 days, the dose of IP was increased to 150 mg if platelet counts were \<100 Gi/L.

DRUGPlacebo

Orally, once daily, beginning on Day 4 of the first cycle of induction. After 7 days, the dose given was matching 300 mg Eltrombopag if platelet counts were \<100 Gi/L. Placebo continued until achievement of platelet count of at least 200 Gi/L or assessment of remission of bone marrow status or a maximum of 42 days after initiation of most recent induction. In subjects of East Asian heritage placebo matching 100 mg Eltrombopag orally once daily was used and after 7 days, the placebo matching 150 mg Eltrombopag was given if platelet counts were \<100 Gi/L.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age \>=18 years * Diagnosed with AML according to the WHO 2008 classification. Note: subjects with secondary AML following Myelodysplastic syndrome or secondary to previous leukemogenic therapy are allowed provided that a record of previous MDS history or leukemogenic therapy history is available. * Eligible for induction by daunorubicin + cytarabine. * Eligible to give informed consent to participate in the study. * Have adequate baseline organ function defined by the following criteria: Total bilirubin \<=1.5 x upper limit of normal (ULN) except for Gilbert's syndrome, or other conditions that are not indicative of inadequate liver function (i.e. elevation of indirect bilirubin (haemolytic) in the absence of alanine aminotransferase \[ALT\] abnormality). ALT \<=3 x ULN. Serum Creatinine \<=2.5 x ULN. * Adequate cardiac function with LVEF \>=50% as assessed by echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA. * Subjects with a QT interval corrected for heart rate according to Bazett's formula (QTcB) \<450millisecond (msec) or \<480msec for subjects with bundle branch block. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period. * Women must be either of non-childbearing potential or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study. * Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of randomization until 30 days after the last dose of investigational product. * Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 30 days following the last dose of investigational product.

Exclusion criteria

* A diagnosis of acute promyelocytic (M3) or acute megakaryocytic leukaemia (M7). * Previous history of exposure to an anthracycline compound. * Previous AML treatment (other than hydroxyurea). * Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent. * History of thromboembolic event or other condition requiring ongoing use of anticoagulation either with warfarin or low molecular-weight heparin. Note: Occlusion of a central line is not exclusion. * Treatment with an investigational drug within 30 days or 5 half lives, whichever is longer, preceding the first dose of study medication. * Current and continued use during study treatment period of known Breast cancer resistance protein (BCRP) inhibitors or known P-gp inhibitors. * Known active hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection. * Known hypersensitivity to any of the study drugs or its excipients.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.	From the time the first dose of study treatment was administered until 30 days following discontinuation of investigational product regardless of initiation of a new cancer therapy or transfer to hospice	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.
Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).	Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	LVEF is a measurement of the percentage of blood leaving heart each time it contracts. LVEF was assessed by an echocardiogram (ECHO) or Multiple Gated Acquisition scan (MUGA). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the Day 42 value minus the Baseline value.
Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The number of participants with a maximum post-baseline grade increase of Grade 3 (G3) or Grade 4 (G4) from their baseline grade are presented. Hematology parameters included only lab tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The number of participants with a maximum post-baseline grade increase of Grade 3 or Grade 4 from their baseline grade are presented. Clinical Clinical Chemistry parameters included only lab tests that are gradable by CTCAE v4.0.
Number of Participants With Liver Events.	8 weeks	The number of participants with liver enzyme (ALT, AST, ALP, Total bilirubin) abnormalities while receiving study treatment in each arm are presented.
Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The number of participants with worst case post-baseline changes (normal, abnormal - not clinically significant \[NCS\], abnormal - clinically significant \[NS\]) in ECG QT prolonged values are presented. The protocol does not define the criteria for normal, abnormal-NCS and abnormal CS ECG. The outcome was based solely on the investigator interpretation of ECG tracings.
Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The number of participants with worst case post-baseline changes (improved, no change, deteriorated) are presented.
Worst-case Change From Baseline in Pulse Rate Values	Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The worst-case post Baseline high and low changes in pulse rate values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Post Baseline is defined as the highest and lowest non-missing post Baseline value respectively. Change from Baseline was calculated as the post Baseline value minus the Baseline value.
Worst-case Post Baseline Change in Blood Pressure Values From Baseline	Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The worst-case post Baseline high changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the visit value minus the Baseline value.
Worst-case Post Baseline Change in Temperature Values From Baseline	Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	The worst-case post Baseline high and low changes in temperature values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Post Baseline was defined as the highest and lowest non-missing post Baseline value respectively. Change from Baseline was calculated as the post Baseline value minus the Baseline value.

Secondary

Measure	Time frame	Description
Daunorubicinol Dose-normalized Plasma: AUC(24-t)	Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)	Daunorubicinol AUC(24-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicin Dose-normalized Plasma: Cmax	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicin Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicinol Dose-normalized Plasma: Cmax	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicinol Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)	Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)	Cycle 2 Daunorubicin AUC(0-24). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)	Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)	Cycle 2 Daunorubicinol AUC(0-24). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax	Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)	Cycle 2 Daunorubicin Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax	Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)	Cycle 2 Daunorubicinol Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Number of Platelet Transfusions Per Week Within Cycles	Post-Base line up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	This was the average number of platelet transfusions per week within cycles.
Time to Platelet Count Recovery >=20 Gi/L	From last dose of chemotherapy to up to end of study year 2 assessment	Time to Platelet counts \>= 20 Gi/L for 3 consecutive days, unaided by transfusions in patients with \< 20 Gi/L after chemotherapy. For this endpoint, the event required platelet count to be \>= 20 Gi/L for 3 consecutive days. Hematology was assessed daily during hospital stay but only weekly after hospital discharge and thus, platelet count was not always available for 3 consecutive days to confirm the achievement of platelet count recovery.
Time to Platelet Recovery >=100 Gi/L	From last dose of chemotherapy to up to end of study year 2 assessment	Time to platelet counts \>= 100 Gi/L unaided by transfusions in participants with \< 100 Gi/L after chemotherapy.
Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicin half-life. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Maximum Duration (Days) of Platelet Transfusion Independence	At differnt time points from start of treatment and up to end of study year 2 assessment	Maximum time period (in days) during which the patient did not receive any platelet transfusion
Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days	From start of treatment and up to end of study year 2 assessment	Percentage of patients who achieved platelet transfusion independence ≥ 28 days.
Time to Neutrophil Engraftment	At different time points from last dose of chemotherapy up to end of study year 2 assessment	Time to absolute neutrophil count (ANC) \>= 0.5 Gi/L for 3 consecutive days in participants with ANC \< 0.5 Gi/L after chemotherapy
Summary of Absolute Neutrophil Counts (ANC)	Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit	Absolute neutrophil counts over time
Summary of Hemoglobin	Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit	Hemoglobin level over time
Incidence of Hemorrhagic Events	Baseline, weekly within induction and re-induction cycles, end of therapy	Incidence of bleeding events using WHO bleeding grade (G0=No bleeding, G1=Petechiae, G2=Mild blood loss, G3=Gross blood loss, G4=Debilitating blood loss) by week and cycle
Percentage of Participants With Disease Response Rate and Type of Response	Day 42 of the latest chemotherapy cycle (Up to 8 weeks)	Disease response as assessed by the investigator using the AML International Working Group Response Assessment at the end of therapy/remission assessment visit; Complete remission (CR): defined as transfusion independence, blood count recovery (Abs. neutrophil count \> 1.0 Gi/L and Platelet count \> 100.0 Gi/L), no leukemic blast in peripheral blood, Bone Marrow (BM) blasts \< 5%, maturation of all cell lines, Auer rods not detectable, and no extramedullary disease. Partial remission (PR): defined as CR except that for BM blasts where a decrease of at least 50% of BM blasts to 5-25% in BM aspirate is sufficient or BM blasts \< 5% with Auer rods present. Overall response (OR) = CR + PR.
Overall Survival (OS)	From randomization to end of 2-year follow-up	Overall survival defined as the time form randomization until the date of death due to any cause.
Number of Participants Who Required Medical Resource Utilization	At screening and from start of treatment to end of therapy/remission assessment visit (Day 42 of the latest chemotherapy cycle)	Medical Resource Utilization pertained to unscheduled hospitalizations, unscheduled office visits, unscheduled laboratory tests, and unscheduled procedures.
Summary of Platelet Counts Over Time	Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit	Platelet counts over time
Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicinol half-life. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicin Dose-normalized Plasma: AUC(0-∞)	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicin AUC(0-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicinol Dose-normalized Plasma: AUC(0-∞)	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicinol AUC(0-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicin Dose-normalized Plasma: AUC(24-∞)	Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)	Daunorubicin AUC(24-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicinol Dose-normalized Plasma: AUC(24-∞)	Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)	Daunorubicinol AUC(24-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicin Dose-normalized Plasma: AUC(0-t)	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	Daunorubicin AUC(0-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Daunorubicinol Dose-normalized Plasma: AUC(0-t)	Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)	daunorubicinol AUC(0-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.
Number of Participants Who Achieved Platelet Count Recovery by Day 21	By Day 21	Number of participants with platelet counts 20 Gi/L for 3 consecutive days, unaided by transfusions, in patients with \< 20 Gi/L after chemotherapy.
Daunorubicin Dose-normalized Plasma: AUC(24-t)	Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)	Daunorubicin AUC(24-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Countries

Australia, Belgium, Canada, Greece, Hungary, Israel, Poland, Russia, South Korea, United States

Participant flow

Recruitment details

Participants (Par.) diagnosed with Acute Myelogenous Leukemia (AML) of any subtype (except acute promyelocytic \[M3\] or acute megakaryocytic leukaemia \[M7\]) were eligible for the study.

Pre-assignment details

Sufficient number of participants were screened and 148 participants were randomized and entered in to the study. Participants were stratified by antecedent malignant hematologic disorder (yes versus no) and age (18-60 years versus \>60 years), before they were randomized to receive study treatments.

Participants by arm

Arm	Count
Eltrombopag (ELQ) QD Par. received IDN CTY consisting of DAU bolus IV INF on D 1-3 at a dose of 90 mg/m\^2 for Par. 18-60 years old or 60 mg/m\^2 for Par.\>60 years old plus cytarabine 100 mg/m\^2 continuous IV INF on D1-7. Par. received ELT as 200 mg (100 mg for East-Asian Heritage) QD oral dose starting on D4 of initial IDN CTY at least 20 hours after end of D3 DAU INF. If PT count was not \>100 Gi/L after 7 days the dose was increased to 300 mg (150 mg East-Asian Heritage) QD until a PT count of at least 200 Gi/L was achieved, until remission was assessed by bone marrow biopsy, or for a maximum of 42 days from the start of the CTY IDN cycle. Par. who were not aplastic after first cycle of IDN CTY received re-IDN with a modified DAU dose of 45mg/m\^2/day on D1-3 plus cytarabine 100 mg/m\^2/day on D1-7. For re-IDN Par., ELT was held from D1-3 of re-IDN, and resumed on D4 at the same dose and duration.	74
Placebo QD Participants received first line IDN CTY consisting of DAU bolus IV INF on Days 1-3 at a dose of 90 mg/m\^2 for participants 18-60 years old or 60 mg/m\^2 for participants \>60 years of age plus cytarabine continuous IV INF on Days 1-7 at a dose of 100 mg/m\^2. Participants received placebo QD oral dose starting on Day 4 of initial IDN CTY at least 20 hours after end of Day 3 DAU INF up to a maximum duration of 42 days.	74
Total	148

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Death	39	30
Overall Study	Lost to Follow-up	4	1
Overall Study	Physician Decision	3	2
Overall Study	Withdrawal by Subject	5	8

Baseline characteristics

Characteristic	Placebo QD	Total	Eltrombopag (ELQ) QD
Age, Continuous	56.6 Years STANDARD_DEVIATION 11.58	56.7 Years STANDARD_DEVIATION 11.88	56.7 Years STANDARD_DEVIATION 12.25
Race/Ethnicity, Customized African American/African Heritage	2 Participants	3 Participants	1 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	17 Participants	43 Participants	26 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	3 Participants	8 Participants	5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	50 Participants	92 Participants	42 Participants
Sex: Female, Male Female	31 Participants	69 Participants	38 Participants
Sex: Female, Male Male	43 Participants	79 Participants	36 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	11 / 74	4 / 71
other Total, other adverse events	71 / 74	66 / 71
serious Total, serious adverse events	24 / 74	14 / 71

Outcome results

Primary

Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).

LVEF is a measurement of the percentage of blood leaving heart each time it contracts. LVEF was assessed by an echocardiogram (ECHO) or Multiple Gated Acquisition scan (MUGA). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the Day 42 value minus the Baseline value.

Time frame: Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Participants in the Safety Population who provided Baseline and Day 42 LVEF measurements.

Arm	Measure	Group	Value (MEAN)	Dispersion
Eltrombopag (ELQ) QD	Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).	chnge from baseline (BL) to end of study	-2.5 LVEF percent	Standard Deviation 7.81
Eltrombopag (ELQ) QD	Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).	change from BL to worse post-BL case	-4.1 LVEF percent	Standard Deviation 8.61
Placebo QD	Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).	chnge from baseline (BL) to end of study	-4.3 LVEF percent	Standard Deviation 8.54
Placebo QD	Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).	change from BL to worse post-BL case	-5.7 LVEF percent	Standard Deviation 9.05

Primary

Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.

Time frame: From the time the first dose of study treatment was administered until 30 days following discontinuation of investigational product regardless of initiation of a new cancer therapy or transfer to hospice

Population: Safety population: all subjects who received at least one dose of investigational product.

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.	Any AE	72 Participants
Eltrombopag (ELQ) QD	Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.	Any SAE	24 Participants
Placebo QD	Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.	Any AE	66 Participants
Placebo QD	Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.	Any SAE	14 Participants

Primary

Number of Participants With Liver Events.

The number of participants with liver enzyme (ALT, AST, ALP, Total bilirubin) abnormalities while receiving study treatment in each arm are presented.

Time frame: 8 weeks

Population: Safety population

Arm	Measure	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants With Liver Events.	2 Participants
Placebo QD	Number of Participants With Liver Events.	6 Participants

Primary

Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values

The number of participants with worst case post-baseline changes (normal, abnormal - not clinically significant \[NCS\], abnormal - clinically significant \[NS\]) in ECG QT prolonged values are presented. The protocol does not define the criteria for normal, abnormal-NCS and abnormal CS ECG. The outcome was based solely on the investigator interpretation of ECG tracings.

Time frame: Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Safety population

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Normal	34 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Abnormal - NCS	23 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Abnormal - CS	2 Participants
Placebo QD	Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Normal	33 Participants
Placebo QD	Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Abnormal - NCS	29 Participants
Placebo QD	Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values	Abnormal - CS	1 Participants

Primary

Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status

The number of participants with worst case post-baseline changes (improved, no change, deteriorated) are presented.

Time frame: Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Participants in the Safety Population who provided Baseline and post-Baseline assessments.

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	Deteriorated	36 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	Improved	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	No Change	37 Participants
Placebo QD	Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	Deteriorated	36 Participants
Placebo QD	Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	Improved	1 Participants
Placebo QD	Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status	No Change	34 Participants

Primary

Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters

The number of participants with a maximum post-baseline grade increase of Grade 3 or Grade 4 from their baseline grade are presented. Clinical Clinical Chemistry parameters included only lab tests that are gradable by CTCAE v4.0.

Time frame: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Safety population

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Alanine Aminotransferase, G3	1 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Albumin, G3	6 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Aspartate Aminotransferase, G3	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Bilirubin, G3	1 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Bilirubin, G4	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Calcium Low, G3	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Creatinine, G3	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Creatinine, G4	1 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Glucose High, G3	6 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Glucose High, G4	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Magnesium Low, G3	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Magnesium High, G3	3 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Phosphate, G3	10 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Phosphate, G4	1 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium Low, G3	8 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium Low, G4	0 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium High, G3	4 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium High, G4	1 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Sodium Low, G3	3 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Urate, G4	3 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium High, G4	1 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Alanine Aminotransferase, G3	5 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Magnesium Low, G3	1 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Albumin, G3	4 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium Low, G4	2 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Aspartate Aminotransferase, G3	1 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Magnesium High, G3	0 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Bilirubin, G3	4 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Urate, G4	0 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Bilirubin, G4	1 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Phosphate, G3	19 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Calcium Low, G3	1 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium High, G3	0 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Creatinine, G3	1 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Phosphate, G4	0 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Creatinine, G4	0 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Sodium Low, G3	4 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Glucose High, G3	3 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Potassium Low, G3	10 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters	Glucose High, G4	1 Participants

Primary

Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters

The number of participants with a maximum post-baseline grade increase of Grade 3 (G3) or Grade 4 (G4) from their baseline grade are presented. Hematology parameters included only lab tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Time frame: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Safety population

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Hemoglobin Low, G3	53 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Leukocytes, G3	10 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Leukocytes, G4	9 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Lymphocytes Low, G3	31 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Lymphocytes Low, G4	35 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Neutrophils, G4	44 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Platelets, G3	1 Participants
Eltrombopag (ELQ) QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Platelets, G4	63 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Platelets, G4	56 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Hemoglobin Low, G3	46 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Lymphocytes Low, G4	38 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Leukocytes, G3	10 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Platelets, G3	0 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Leukocytes, G4	5 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Neutrophils, G4	39 Participants
Placebo QD	Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters	Lymphocytes Low, G3	26 Participants

Primary

Worst-case Change From Baseline in Pulse Rate Values

The worst-case post Baseline high and low changes in pulse rate values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Post Baseline is defined as the highest and lowest non-missing post Baseline value respectively. Change from Baseline was calculated as the post Baseline value minus the Baseline value.

Time frame: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Safety population. Only those participants available at the indicated time points were analyzed (represented by n=X, X in the category titles)

Arm	Measure	Group	Value (MEAN)	Dispersion
Eltrombopag (ELQ) QD	Worst-case Change From Baseline in Pulse Rate Values	High	18.48 Beats/minute	Standard Deviation 20.616
Eltrombopag (ELQ) QD	Worst-case Change From Baseline in Pulse Rate Values	Low	-10.36 Beats/minute	Standard Deviation 14.039
Placebo QD	Worst-case Change From Baseline in Pulse Rate Values	High	17.73 Beats/minute	Standard Deviation 15.112
Placebo QD	Worst-case Change From Baseline in Pulse Rate Values	Low	-11.24 Beats/minute	Standard Deviation 12.123

Primary

Worst-case Post Baseline Change in Blood Pressure Values From Baseline

The worst-case post Baseline high changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the visit value minus the Baseline value.

Time frame: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Safety population

Arm	Measure	Group	Value (MEAN)	Dispersion
Eltrombopag (ELQ) QD	Worst-case Post Baseline Change in Blood Pressure Values From Baseline	SBP	14.59 millimeter of mercury (mmHg)	Standard Deviation 17.936
Eltrombopag (ELQ) QD	Worst-case Post Baseline Change in Blood Pressure Values From Baseline	DBP	9.38 millimeter of mercury (mmHg)	Standard Deviation 12
Placebo QD	Worst-case Post Baseline Change in Blood Pressure Values From Baseline	SBP	14.34 millimeter of mercury (mmHg)	Standard Deviation 14.626
Placebo QD	Worst-case Post Baseline Change in Blood Pressure Values From Baseline	DBP	12.61 millimeter of mercury (mmHg)	Standard Deviation 10.947

Primary

Worst-case Post Baseline Change in Temperature Values From Baseline

The worst-case post Baseline high and low changes in temperature values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Post Baseline was defined as the highest and lowest non-missing post Baseline value respectively. Change from Baseline was calculated as the post Baseline value minus the Baseline value.

Time frame: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Population: Safety population. Only those participants available at the indicated time points were analyzed (represented by n=X, X in the category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Eltrombopag (ELQ) QD	Worst-case Post Baseline Change in Temperature Values From Baseline	High	0.62 Degrees Celsius	Standard Deviation 0.941
Eltrombopag (ELQ) QD	Worst-case Post Baseline Change in Temperature Values From Baseline	Low	-0.44 Degrees Celsius	Standard Deviation 0.628
Placebo QD	Worst-case Post Baseline Change in Temperature Values From Baseline	High	0.77 Degrees Celsius	Standard Deviation 0.879
Placebo QD	Worst-case Post Baseline Change in Temperature Values From Baseline	Low	-0.63 Degrees Celsius	Standard Deviation 0.592

Secondary

Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)

Cycle 2 Daunorubicin AUC(0-24). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)	10.315 (h*ug/ml)/(mg/m2)
Placebo QD	Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)	8.1146 (h*ug/ml)/(mg/m2)

90% CI: [84.2, 191.9]

Secondary

Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax

Cycle 2 Daunorubicin Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax	11.141 (ug/ml)/(mg/m2)
Placebo QD	Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax	3.8905 (ug/ml)/(mg/m2)

90% CI: [90.1, 910.7]

Secondary

Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)

Cycle 2 Daunorubicinol AUC(0-24). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)	34.067 (h*ug/ml)/(mg/m2)
Placebo QD	Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)	30.820 (h*ug/ml)/(mg/m2)

90% CI: [83.9, 145.7]

Secondary

Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax

Cycle 2 Daunorubicinol Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax	4.0200 (ug/ml)/(mg/m2)
Placebo QD	Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax	1.9868 (ug/ml)/(mg/m2)

90% CI: [131.3, 311.8]

Secondary

Daunorubicin Dose-normalized Plasma: AUC(0-∞)

Daunorubicin AUC(0-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicin Dose-normalized Plasma: AUC(0-∞)	8.0807 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicin Dose-normalized Plasma: AUC(0-∞)	8.7880 (h*ug/ml)/(mg/m2)

90% CI: [76.8, 110.2]

Secondary

Daunorubicin Dose-normalized Plasma: AUC(0-t)

Daunorubicin AUC(0-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicin Dose-normalized Plasma: AUC(0-t)	7.9523 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicin Dose-normalized Plasma: AUC(0-t)	8.6723 (h*ug/ml)/(mg/m2)

90% CI: [76.5, 110]

Secondary

Daunorubicin Dose-normalized Plasma: AUC(24-∞)

Daunorubicin AUC(24-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicin Dose-normalized Plasma: AUC(24-∞)	0.87496 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicin Dose-normalized Plasma: AUC(24-∞)	0.72315 (h*ug/ml)/(mg/m2)

90% CI: [102.5, 142.8]

Secondary

Daunorubicin Dose-normalized Plasma: AUC(24-t)

Daunorubicin AUC(24-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicin Dose-normalized Plasma: AUC(24-t)	0.76524 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicin Dose-normalized Plasma: AUC(24-t)	0.59660 (h*ug/ml)/(mg/m2)

90% CI: [100.7, 142.6]

Secondary

Daunorubicin Dose-normalized Plasma: Cmax

Daunorubicin Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicin Dose-normalized Plasma: Cmax	5.1527 (ug/ml)/(mg/m2)
Placebo QD	Daunorubicin Dose-normalized Plasma: Cmax	6.4113 (ug/ml)/(mg/m2)

90% CI: [57.2, 113]

Secondary

Daunorubicinol Dose-normalized Plasma: AUC(0-∞)

Daunorubicinol AUC(0-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicinol Dose-normalized Plasma: AUC(0-∞)	63.997 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicinol Dose-normalized Plasma: AUC(0-∞)	62.835 (h*ug/ml)/(mg/m2)

90% CI: [92.9, 111.7]

Secondary

Daunorubicinol Dose-normalized Plasma: AUC(0-t)

daunorubicinol AUC(0-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicinol Dose-normalized Plasma: AUC(0-t)	62.463 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicinol Dose-normalized Plasma: AUC(0-t)	61.608 (h*ug/ml)/(mg/m2)

90% CI: [92.4, 111.2]

Secondary

Daunorubicinol Dose-normalized Plasma: AUC(24-∞)

Daunorubicinol AUC(24-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicinol Dose-normalized Plasma: AUC(24-∞)	24.537 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicinol Dose-normalized Plasma: AUC(24-∞)	23.039 (h*ug/ml)/(mg/m2)

90% CI: [95, 119.4]

Secondary

Daunorubicinol Dose-normalized Plasma: AUC(24-t)

Daunorubicinol AUC(24-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicinol Dose-normalized Plasma: AUC(24-t)	22.963 (h*ug/ml)/(mg/m2)
Placebo QD	Daunorubicinol Dose-normalized Plasma: AUC(24-t)	21.821 (h*ug/ml)/(mg/m2)

90% CI: [93.6, 118.3]

Secondary

Daunorubicinol Dose-normalized Plasma: Cmax

Daunorubicinol Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Daunorubicinol Dose-normalized Plasma: Cmax	3.5770 (ug/ml)/(mg/m2)
Placebo QD	Daunorubicinol Dose-normalized Plasma: Cmax	3.3640 (ug/ml)/(mg/m2)

90% CI: [87.6, 129]

Secondary

Incidence of Hemorrhagic Events

Incidence of bleeding events using WHO bleeding grade (G0=No bleeding, G1=Petechiae, G2=Mild blood loss, G3=Gross blood loss, G4=Debilitating blood loss) by week and cycle

Time frame: Baseline, weekly within induction and re-induction cycles, end of therapy

Population: The Intent-to-Treat (ITT) population comprised all randomized subjects regardless of whether or not study treatment was administered. This population was based on the treatment to which the subject was randomized.

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 2	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 0	36 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 0	12 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 0	8 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 1	9 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 1	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 1	2 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 2	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 1	13 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 2	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 0	7 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 1	16 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 1	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 2	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 2	3 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 3	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 0	5 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 1	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 2	5 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 2	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 0	31 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 0	8 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 0	3 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 2	5 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 1	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 1	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 2	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 1	4 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 2	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 3	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	Remission visit GRADE 0	56 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 2	2 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	Remission visit GRADE 1	2 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 0	9 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	Remission visit GRADE 2	3 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 0	42 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	Remission visit GRADE 3	1 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 1	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 3	0 Participants
Eltrombopag (ELQ) QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 0	58 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D42 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D42 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	Remission visit GRADE 0	58 Participants
Placebo QD	Incidence of Hemorrhagic Events	Remission visit GRADE 1	4 Participants
Placebo QD	Incidence of Hemorrhagic Events	Remission visit GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	Remission visit GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D42 - GRADE 0	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D42 - GRADE 1	1 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 0	47 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 1	16 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 2	6 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D7 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 0	43 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 1	13 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 2	6 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D14 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 0	43 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 1	7 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 2	1 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D21 - GRADE 3	1 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 0	25 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 1	3 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D28 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 0	11 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 1	2 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D35 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D42 - GRADE 0	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D42 - GRADE 1	1 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D42 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C1D42 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 0	8 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 1	4 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D1 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 0	8 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 1	3 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D7 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 0	7 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 1	3 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D14 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 0	7 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 1	2 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D21 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 0	7 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 1	1 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 2	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D28 - GRADE 3	0 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 0	2 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 1	1 Participants
Placebo QD	Incidence of Hemorrhagic Events	C2D35 - GRADE 2	0 Participants

Secondary

Maximum Duration (Days) of Platelet Transfusion Independence

Maximum time period (in days) during which the patient did not receive any platelet transfusion

Time frame: At differnt time points from start of treatment and up to end of study year 2 assessment

Arm	Measure	Value (MEDIAN)
Eltrombopag (ELQ) QD	Maximum Duration (Days) of Platelet Transfusion Independence	29.0 Days
Placebo QD	Maximum Duration (Days) of Platelet Transfusion Independence	29.5 Days

p-value: 0.6942Wilcoxon rank-sum test

Secondary

Number of Participants Who Achieved Platelet Count Recovery by Day 21

Number of participants with platelet counts 20 Gi/L for 3 consecutive days, unaided by transfusions, in patients with \< 20 Gi/L after chemotherapy.

Time frame: By Day 21

Arm	Measure	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants Who Achieved Platelet Count Recovery by Day 21	4 Count of participants
Placebo QD	Number of Participants Who Achieved Platelet Count Recovery by Day 21	7 Count of participants

p-value: 0.322495% CI: [0.1084, 2.2086]Cochran-Mantel-Haenszel

Secondary

Number of Participants Who Required Medical Resource Utilization

Medical Resource Utilization pertained to unscheduled hospitalizations, unscheduled office visits, unscheduled laboratory tests, and unscheduled procedures.

Time frame: At screening and from start of treatment to end of therapy/remission assessment visit (Day 42 of the latest chemotherapy cycle)

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Number of Participants Who Required Medical Resource Utilization	In-patient hospitalizations/ admissions?	3 Count of participants
Eltrombopag (ELQ) QD	Number of Participants Who Required Medical Resource Utilization	Diagnostic imaging procedures performed?	3 Count of participants
Eltrombopag (ELQ) QD	Number of Participants Who Required Medical Resource Utilization	Health care resources use or emergency visits?	8 Count of participants
Eltrombopag (ELQ) QD	Number of Participants Who Required Medical Resource Utilization	Out-patient lab tests performed?	6 Count of participants
Placebo QD	Number of Participants Who Required Medical Resource Utilization	Out-patient lab tests performed?	6 Count of participants
Placebo QD	Number of Participants Who Required Medical Resource Utilization	In-patient hospitalizations/ admissions?	4 Count of participants
Placebo QD	Number of Participants Who Required Medical Resource Utilization	Health care resources use or emergency visits?	6 Count of participants
Placebo QD	Number of Participants Who Required Medical Resource Utilization	Diagnostic imaging procedures performed?	4 Count of participants

Secondary

Number of Platelet Transfusions Per Week Within Cycles

This was the average number of platelet transfusions per week within cycles.

Time frame: Post-Base line up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Arm	Measure	Value (MEDIAN)	Dispersion
Eltrombopag (ELQ) QD	Number of Platelet Transfusions Per Week Within Cycles	1.5 Platelet transfusions per week	Standard Deviation 1.18
Placebo QD	Number of Platelet Transfusions Per Week Within Cycles	1.4 Platelet transfusions per week	Standard Deviation 1.22

Secondary

Overall Survival (OS)

Overall survival defined as the time form randomization until the date of death due to any cause.

Time frame: From randomization to end of 2-year follow-up

Arm	Measure	Value (NUMBER)
Eltrombopag (ELQ) QD	Overall Survival (OS)	39 Count of participants
Placebo QD	Overall Survival (OS)	30 Count of participants

p-value: 0.068895% CI: [0.96, 2.47]Log Rank

Secondary

Percentage of Participants With Disease Response Rate and Type of Response

Disease response as assessed by the investigator using the AML International Working Group Response Assessment at the end of therapy/remission assessment visit; Complete remission (CR): defined as transfusion independence, blood count recovery (Abs. neutrophil count \> 1.0 Gi/L and Platelet count \> 100.0 Gi/L), no leukemic blast in peripheral blood, Bone Marrow (BM) blasts \< 5%, maturation of all cell lines, Auer rods not detectable, and no extramedullary disease. Partial remission (PR): defined as CR except that for BM blasts where a decrease of at least 50% of BM blasts to 5-25% in BM aspirate is sufficient or BM blasts \< 5% with Auer rods present. Overall response (OR) = CR + PR.

Time frame: Day 42 of the latest chemotherapy cycle (Up to 8 weeks)

Arm	Measure	Group	Value (NUMBER)
Eltrombopag (ELQ) QD	Percentage of Participants With Disease Response Rate and Type of Response	Overall response	70 Percentage of participants
Eltrombopag (ELQ) QD	Percentage of Participants With Disease Response Rate and Type of Response	Complete Remission (CR)	65 Percentage of participants
Eltrombopag (ELQ) QD	Percentage of Participants With Disease Response Rate and Type of Response	Partial Remission (PR)	5 Percentage of participants
Placebo QD	Percentage of Participants With Disease Response Rate and Type of Response	Overall response	73 Percentage of participants
Placebo QD	Percentage of Participants With Disease Response Rate and Type of Response	Complete Remission (CR)	70 Percentage of participants
Placebo QD	Percentage of Participants With Disease Response Rate and Type of Response	Partial Remission (PR)	3 Percentage of participants

p-value: 0.712295% CI: [0.4023, 1.8943]Cochran-Mantel-Haenszel

Secondary

Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days

Percentage of patients who achieved platelet transfusion independence ≥ 28 days.

Time frame: From start of treatment and up to end of study year 2 assessment

Arm	Measure	Value (NUMBER)
Eltrombopag (ELQ) QD	Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days	55 Percentage of participants
Placebo QD	Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days	53 Percentage of participants

p-value: 0.739795% CI: [0.5585, 2.229]Cochran-Mantel-Haenszel

Secondary

Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)

Daunorubicin half-life. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)	15.754 hour (h)
Placebo QD	Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)	13.709 hour (h)

90% CI: [99.5, 132.7]

Secondary

Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)

Daunorubicinol half-life. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2.

Time frame: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)

Population: PK population: The PK population consisted of all subjects who completed initial induction treatment and had at least 1 non-baseline blood sample for PK obtained and analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)
Eltrombopag (ELQ) QD	Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)	22.735 hour (h)
Placebo QD	Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)	21.603 hour (h)

90% CI: [97.1, 114]

Secondary

Summary of Absolute Neutrophil Counts (ANC)

Absolute neutrophil counts over time

Time frame: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit

Arm	Measure	Group	Value (MEDIAN)
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D6	0.2 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D28	4.3 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D2	0.6 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D35	2.2 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D7	0.1 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D4	0.4 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D1	0.1 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D8	0.1 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D2	0.1 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D1	0.8 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D3	0.2 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D9	0.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D4	0.3 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D5	0.3 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D5	0.2 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D14	0.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D6	0.1 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D3	0.6 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D7	0.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C1D21	0.6 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	C2D14	0.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Absolute Neutrophil Counts (ANC)	Baseline	0.8 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D7	0.1 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D14	0.0 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	Baseline	0.5 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D1	0.6 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D2	0.5 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D3	0.4 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D4	0.2 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D5	0.2 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D6	0.1 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D7	0.1 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D8	0.0 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D9	0.0 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D14	0.0 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D21	0.3 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D28	2.7 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D35	1.7 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C1D42	3.1 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D1	0.0 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D2	0.2 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D3	0.5 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D4	0.5 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D5	0.1 Gi/L
Placebo QD	Summary of Absolute Neutrophil Counts (ANC)	C2D6	0.1 Gi/L

Secondary

Summary of Hemoglobin

Hemoglobin level over time

Time frame: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit

Arm	Measure	Group	Value (MEDIAN)
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D6	84.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D1	88.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D2	88.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D3	86.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D4	83.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D5	84.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D6	86.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D7	85.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D8	85.3 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D9	84.5 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D14	85.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D21	88.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D28	99.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C1D35	99.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D1	94.5 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D2	88.5 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D3	86.5 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D4	89.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D5	88.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	Baseline	87.6 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D7	84.5 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D14	77.5 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D21	86.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D28	89.0 g/L
Eltrombopag (ELQ) QD	Summary of Hemoglobin	C2D35	104.0 g/L
Placebo QD	Summary of Hemoglobin	C1D28	98.0 g/L
Placebo QD	Summary of Hemoglobin	C2D6	85.0 g/L
Placebo QD	Summary of Hemoglobin	C1D35	94.0 g/L
Placebo QD	Summary of Hemoglobin	Baseline	87.0 g/L
Placebo QD	Summary of Hemoglobin	C1D42	98.0 g/L
Placebo QD	Summary of Hemoglobin	C1D1	86.0 g/L
Placebo QD	Summary of Hemoglobin	C2D35	87.0 g/L
Placebo QD	Summary of Hemoglobin	C1D2	83.0 g/L
Placebo QD	Summary of Hemoglobin	C2D1	82.5 g/L
Placebo QD	Summary of Hemoglobin	C1D3	82.0 g/L
Placebo QD	Summary of Hemoglobin	C2D7	83.0 g/L
Placebo QD	Summary of Hemoglobin	C1D4	81.5 g/L
Placebo QD	Summary of Hemoglobin	C2D2	86.5 g/L
Placebo QD	Summary of Hemoglobin	C1D5	83.0 g/L
Placebo QD	Summary of Hemoglobin	C2D28	80.0 g/L
Placebo QD	Summary of Hemoglobin	C1D6	82.0 g/L
Placebo QD	Summary of Hemoglobin	C2D3	80.0 g/L
Placebo QD	Summary of Hemoglobin	C1D7	83.0 g/L
Placebo QD	Summary of Hemoglobin	C2D14	87.0 g/L
Placebo QD	Summary of Hemoglobin	C1D8	84.0 g/L
Placebo QD	Summary of Hemoglobin	C2D4	86.5 g/L
Placebo QD	Summary of Hemoglobin	C1D9	81.5 g/L
Placebo QD	Summary of Hemoglobin	C2D42	90.5 g/L
Placebo QD	Summary of Hemoglobin	C1D14	84.0 g/L
Placebo QD	Summary of Hemoglobin	C2D5	84.0 g/L
Placebo QD	Summary of Hemoglobin	C1D21	88.0 g/L
Placebo QD	Summary of Hemoglobin	C2D21	91.0 g/L

Secondary

Summary of Platelet Counts Over Time

Platelet counts over time

Time frame: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit

Arm	Measure	Group	Value (MEDIAN)
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D5	33.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D2	43.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D6	32.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D2	26.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D8	24.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D3	25.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D7	27.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D4	32.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D9	20.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D5	37.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D3	35.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D6	27.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D14	16.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D7	24.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D1	52.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D14	10.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D21	39.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D21	27.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D4	36.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D28	68.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D28	484.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D35	515.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	Baseline	51.5 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C1D35	547.0 Gi/L
Eltrombopag (ELQ) QD	Summary of Platelet Counts Over Time	C2D1	31.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D35	272.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D42	147.5 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D21	38.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D7	27.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	Baseline	50.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D1	48.5 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D2	42.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D3	37.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D4	29.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D5	29.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D8	22.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D9	19.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D14	18.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D21	25.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D28	121.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D35	181.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D42	304.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D1	30.5 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D2	28.5 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D3	29.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D4	35.5 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D5	22.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D6	33.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D7	28.5 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D14	16.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C1D6	30.0 Gi/L
Placebo QD	Summary of Platelet Counts Over Time	C2D28	173.0 Gi/L

Secondary

Time to Neutrophil Engraftment

Time to absolute neutrophil count (ANC) \>= 0.5 Gi/L for 3 consecutive days in participants with ANC \< 0.5 Gi/L after chemotherapy

Time frame: At different time points from last dose of chemotherapy up to end of study year 2 assessment

Arm	Measure	Value (MEDIAN)
Eltrombopag (ELQ) QD	Time to Neutrophil Engraftment	NA Months
Placebo QD	Time to Neutrophil Engraftment	NA Months

p-value: 0.078195% CI: [0.95, 6.38]Log Rank

Secondary

Time to Platelet Count Recovery >=20 Gi/L

Time to Platelet counts \>= 20 Gi/L for 3 consecutive days, unaided by transfusions in patients with \< 20 Gi/L after chemotherapy. For this endpoint, the event required platelet count to be \>= 20 Gi/L for 3 consecutive days. Hematology was assessed daily during hospital stay but only weekly after hospital discharge and thus, platelet count was not always available for 3 consecutive days to confirm the achievement of platelet count recovery.

Time frame: From last dose of chemotherapy to up to end of study year 2 assessment

Arm	Measure	Value (MEDIAN)
Eltrombopag (ELQ) QD	Time to Platelet Count Recovery >=20 Gi/L	NA Months
Placebo QD	Time to Platelet Count Recovery >=20 Gi/L	NA Months

p-value: 0.746195% CI: [0.28, 2.48]Log Rank

Secondary

Time to Platelet Recovery >=100 Gi/L

Time to platelet counts \>= 100 Gi/L unaided by transfusions in participants with \< 100 Gi/L after chemotherapy.

Time frame: From last dose of chemotherapy to up to end of study year 2 assessment

Arm	Measure	Value (MEDIAN)
Eltrombopag (ELQ) QD	Time to Platelet Recovery >=100 Gi/L	0.69 Months
Placebo QD	Time to Platelet Recovery >=100 Gi/L	0.69 Months

p-value: 0.617595% CI: [0.74, 1.63]Log Rank

Source: ClinicalTrials.gov · Data processed: Mar 4, 2026

A Safety and Efficacy Study of Eltrombopag in Subjects With AML

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).

Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.

Number of Participants With Liver Events.

Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values

Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status

Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters

Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters

Worst-case Change From Baseline in Pulse Rate Values

Worst-case Post Baseline Change in Blood Pressure Values From Baseline

Worst-case Post Baseline Change in Temperature Values From Baseline

Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)

Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax

Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)

Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax

Daunorubicin Dose-normalized Plasma: AUC(0-∞)

Daunorubicin Dose-normalized Plasma: AUC(0-t)

Daunorubicin Dose-normalized Plasma: AUC(24-∞)

Daunorubicin Dose-normalized Plasma: AUC(24-t)

Daunorubicin Dose-normalized Plasma: Cmax

Daunorubicinol Dose-normalized Plasma: AUC(0-∞)

Daunorubicinol Dose-normalized Plasma: AUC(0-t)

Daunorubicinol Dose-normalized Plasma: AUC(24-∞)

Daunorubicinol Dose-normalized Plasma: AUC(24-t)

Daunorubicinol Dose-normalized Plasma: Cmax

Incidence of Hemorrhagic Events

Maximum Duration (Days) of Platelet Transfusion Independence

Number of Participants Who Achieved Platelet Count Recovery by Day 21

Number of Participants Who Required Medical Resource Utilization

Number of Platelet Transfusions Per Week Within Cycles

Overall Survival (OS)

Percentage of Participants With Disease Response Rate and Type of Response

Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days

Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)

Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)

Summary of Absolute Neutrophil Counts (ANC)

Summary of Hemoglobin

Summary of Platelet Counts Over Time

Time to Neutrophil Engraftment

Time to Platelet Count Recovery >=20 Gi/L

Time to Platelet Recovery >=100 Gi/L