A Safety and Efficacy Study of Eltrombopag in Subjects With AML

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01890746

Collaborator

(none)

148

Enrollment

Locations

Arms

40.7

Actual Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Leukaemia	Drug: Daunorubicin Drug: Cytarabine Drug: Eltrombopag Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

148 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 5, 2013

Actual Primary Completion Date :

Mar 13, 2015

Actual Study Completion Date :

Jan 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eltrombopag arm Subjects received induction chemotherapy consisting of daunorubicin bolus intravenous (IV) infusion on Days 1-3 + cytarabine continuous IV infusion on Days 1-7 followed by Eltrombopag once daily orally starting on Day 4 of initial induction chemotherapy. If platelet count was not greater than 100 Gi/L after 7 days the dose was increased until a platelet count of at least 200 Gi/L was achieved/until remission was assessed/ maximum of 42 days from the start of the chemotherapy induction. Subjects who were not aplastic after first cycle of induction chemotherapy received second induction chemotherapy with a modified daunorubicin dose on Days 1-3 + cytarabine on Days 1-7.	Drug: Daunorubicin 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. Drug: Cytarabine 100 mg/m2/day continuous IV infusion on Days 1 through 7. Drug: Eltrombopag 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.
Placebo Comparator: Placebo arm Subject received induction chemotherapy consisting of daunorubicin bolus IV infusion on Days 1-3 + cytarabine continuous IV infusion on Days 1-7 followed by matching placebo once daily oral dose starting on Day 4 of initial induction chemotherapy. If platelet count was not greater than 100 Gi/L after 7 days the matching placebo was given until a platelet count of at least 200 Gi/L was achieved/ until remission was assessed/ maximum of 42 days from the start of the chemotherapy induction. Subjects who were not aplastic after first cycle of induction chemotherapy received a second induction chemotherapy with a modified daunorubicin dose on Days 1-3 + cytarabine on Days 1-7.	Drug: Daunorubicin 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. Drug: Cytarabine 100 mg/m2/day continuous IV infusion on Days 1 through 7. Drug: Placebo 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.

Arm

Intervention/Treatment

Experimental: Eltrombopag arm

Subjects received induction chemotherapy consisting of daunorubicin bolus intravenous (IV) infusion on Days 1-3 + cytarabine continuous IV infusion on Days 1-7 followed by Eltrombopag once daily orally starting on Day 4 of initial induction chemotherapy. If platelet count was not greater than 100 Gi/L after 7 days the dose was increased until a platelet count of at least 200 Gi/L was achieved/until remission was assessed/ maximum of 42 days from the start of the chemotherapy induction. Subjects who were not aplastic after first cycle of induction chemotherapy received second induction chemotherapy with a modified daunorubicin dose on Days 1-3 + cytarabine on Days 1-7.

Drug: Daunorubicin

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.

Drug: Cytarabine

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

Drug: Eltrombopag

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.

Placebo Comparator: Placebo arm

Subject received induction chemotherapy consisting of daunorubicin bolus IV infusion on Days 1-3 + cytarabine continuous IV infusion on Days 1-7 followed by matching placebo once daily oral dose starting on Day 4 of initial induction chemotherapy. If platelet count was not greater than 100 Gi/L after 7 days the matching placebo was given until a platelet count of at least 200 Gi/L was achieved/ until remission was assessed/ maximum of 42 days from the start of the chemotherapy induction. Subjects who were not aplastic after first cycle of induction chemotherapy received a second induction chemotherapy with a modified daunorubicin dose on Days 1-3 + cytarabine on Days 1-7.

Drug: Daunorubicin

Drug: Cytarabine

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

Drug: Placebo

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
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.
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.
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.
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
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Farmington	Connecticut	United States	06030-1628
2	Novartis Investigative Site	Miami	Florida	United States	33136
3	Novartis Investigative Site	Orlando	Florida	United States	32806
4	Novartis Investigative Site	Atlanta	Georgia	United States	30322
5	Novartis Investigative Site	Ames	Iowa	United States	50010
6	Novartis Investigative Site	Sioux City	Iowa	United States	51101-1733
7	Novartis Investigative Site	Burlington	Massachusetts	United States	01805
8	Novartis Investigative Site	Kansas City	Missouri	United States	64128
9	Novartis Investigative Site	Rochester	New York	United States	14642
10	Novartis Investigative Site	Durham	North Carolina	United States	22713
11	Novartis Investigative Site	Canton	Ohio	United States	44710
12	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19104
13	Novartis Investigative Site	Providence	Rhode Island	United States	02903
14	Novartis Investigative Site	Nashville	Tennessee	United States	37232
15	Novartis Investigative Site	Kogarah	New South Wales	Australia	2217
16	Novartis Investigative Site	Melbourne	Victoria	Australia	3004
17	Novartis Investigative Site	Parkville	Victoria	Australia	3050
18	Novartis Investigative Site	Bruxelles		Belgium	1070
19	Novartis Investigative Site	Leuven		Belgium	3000
20	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
21	Novartis Investigative Site	Montreal	Quebec	Canada	H2L 4M1
22	Novartis Investigative Site	Athens		Greece	11527
23	Novartis Investigative Site	Patra		Greece	26500
24	Novartis Investigative Site	Debrecen		Hungary	4012
25	Novartis Investigative Site	Szeged		Hungary	6720
26	Novartis Investigative Site	Haifa		Israel	31096
27	Novartis Investigative Site	Holon		Israel	58100
28	Novartis Investigative Site	Jerusalem		Israel	91031
29	Novartis Investigative Site	Jerusalem		Israel	91120
30	Novartis Investigative Site	Kfar Saba		Israel	44281
31	Novartis Investigative Site	Tel-Aviv		Israel	64239
32	Novartis Investigative Site	Seoul, Korea		Korea, Republic of	137-701
33	Novartis Investigative Site	Seoul		Korea, Republic of	135-710
34	Novartis Investigative Site	Seoul		Korea, Republic of	138-736
35	Novartis Investigative Site	Slupsk		Poland	76-200
36	Novartis Investigative Site	Wroclaw		Poland	50-367
37	Novartis Investigative Site	Kaluga		Russian Federation	248007
38	Novartis Investigative Site	Moscow		Russian Federation	115478
39	Novartis Investigative Site	Nizhniy Novgorod		Russian Federation	603126
40	Novartis Investigative Site	Penza		Russian Federation	440071
41	Novartis Investigative Site	St'Petersburg		Russian Federation	197341
42	Novartis Investigative Site	Tula		Russian Federation	300053

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01890746

Other Study ID Numbers:

117146
2013-000642-20

First Posted:

Jul 2, 2013

Last Update Posted:

Sep 11, 2019

Last Verified:

Aug 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

acute myeloid leukemia

acute myelogenous leukemia (AML)

secondary acute myeloid leukemia

ETB115

Eltrombopag

thrombocytopenia

oral thrombopoietin receptor agonist

Additional relevant MeSH terms:

Leukemia

Cytarabine

Daunorubicin

Study Results

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 Detail	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.

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	74	74
COMPLETED	22	33
NOT COMPLETED	52	41

Baseline Characteristics

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	74	74	148
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.7 (12.25)	56.6 (11.58)	56.7 (11.88)
Sex: Female, Male (Count of Participants)
Female	38 51.4%	31 41.9%	69 46.6%
Male	36 48.6%	43 58.1%	79 53.4%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	1 1.4%	2 2.7%	3 2%
Asian - Central/South Asian Heritage	0 0%	1 1.4%	1 0.7%
Asian - East Asian Heritage	26 35.1%	17 23%	43 29.1%
Asian - South East Asian Heritage	0 0%	1 1.4%	1 0.7%
White - Arabic/North African Heritage	5 6.8%	3 4.1%	8 5.4%
White - White/Caucasian/European Heritage	42 56.8%	50 67.6%	92 62.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
Any AE	72 97.3%	66 89.2%
Any SAE	24 32.4%	14 18.9%

2. Primary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
chnge from baseline (BL) to end of study	-2.5 (7.81)	-4.3 (8.54)
change from BL to worse post-BL case	-4.1 (8.61)	-5.7 (9.05)

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
Hemoglobin Low, G3	53 71.6%	46 62.2%
Leukocytes, G3	10 13.5%	10 13.5%
Leukocytes, G4	9 12.2%	5 6.8%
Lymphocytes Low, G3	31 41.9%	26 35.1%
Lymphocytes Low, G4	35 47.3%	38 51.4%
Neutrophils, G4	44 59.5%	39 52.7%
Platelets, G3	1 1.4%	0 0%
Platelets, G4	63 85.1%	56 75.7%

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
Alanine Aminotransferase, G3	1 1.4%	5 6.8%
Albumin, G3	6 8.1%	4 5.4%
Aspartate Aminotransferase, G3	0 0%	1 1.4%
Bilirubin, G3	1 1.4%	4 5.4%
Bilirubin, G4	0 0%	1 1.4%
Calcium Low, G3	0 0%	1 1.4%
Creatinine, G3	0 0%	1 1.4%
Creatinine, G4	1 1.4%	0 0%
Glucose High, G3	6 8.1%	3 4.1%
Glucose High, G4	0 0%	1 1.4%
Magnesium Low, G3	0 0%	1 1.4%
Magnesium High, G3	3 4.1%	0 0%
Phosphate, G3	10 13.5%	19 25.7%
Phosphate, G4	1 1.4%	0 0%
Potassium Low, G3	8 10.8%	10 13.5%
Potassium Low, G4	0 0%	2 2.7%
Potassium High, G3	4 5.4%	0 0%
Potassium High, G4	1 1.4%	1 1.4%
Sodium Low, G3	3 4.1%	4 5.4%
Urate, G4	3 4.1%	0 0%

5. Primary Outcome

Title	Number of Participants With Liver Events.
Description	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

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
Number [Participants]	2 2.7%	6 8.1%

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
Normal	34 45.9%	33 44.6%
Abnormal - NCS	23 31.1%	29 39.2%
Abnormal - CS	2 2.7%	1 1.4%

7. Primary Outcome

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

Outcome Measure Data

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

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
Deteriorated	36 48.6%	36 48.6%
Improved	0 0%	1 1.4%
No Change	37 50%	34 45.9%

8. Primary Outcome

Title	Worst-case Change From Baseline in Pulse Rate Values
Description	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)

Outcome Measure Data

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

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
High	18.48 (20.616)	17.73 (15.112)
Low	-10.36 (14.039)	-11.24 (12.123)

9. Primary Outcome

Title	Worst-case Post Baseline Change in Blood Pressure Values From Baseline
Description	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)

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
SBP	14.59 (17.936)	14.34 (14.626)
DBP	9.38 (12.000)	12.61 (10.947)

10. Primary Outcome

Title	Worst-case Post Baseline Change in Temperature Values From Baseline
Description	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)

Outcome Measure Data

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

Arm/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	71
High	0.62 (0.941)	0.77 (0.879)
Low	-0.44 (0.628)	-0.63 (0.592)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [hour (h)]	15.754	13.709

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	114.9
	Confidence Interval	(2-Sided) 90% 99.5 to 132.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [hour (h)]	22.735	21.603

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	105.2
	Confidence Interval	(2-Sided) 90% 97.1 to 114.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	8.0807	8.7880

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	92.0
	Confidence Interval	(2-Sided) 90% 76.8 to 110.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	63.997	62.835

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	101.8
	Confidence Interval	(2-Sided) 90% 92.9 to 111.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	0.87496	0.72315

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	121.0
	Confidence Interval	(2-Sided) 90% 102.5 to 142.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	24.537	23.039

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	106.5
	Confidence Interval	(2-Sided) 90% 95.0 to 119.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	7.9523	8.6723

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	91.7
	Confidence Interval	(2-Sided) 90% 76.5 to 110.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	62.463	61.608

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	101.4
	Confidence Interval	(2-Sided) 90% 92.4 to 111.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	0.76524	0.59660

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	120.0
	Confidence Interval	(2-Sided) 90% 100.7 to 142.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (90% Confidence Interval) [(h*ug/ml)/(mg/m2)]	22.963	21.821

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	105.2
	Confidence Interval	(2-Sided) 90% 93.6 to 118.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Daunorubicin Dose-normalized Plasma: Cmax
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(ug/ml)/(mg/m2)]	5.1527	6.4113

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	80.4
	Confidence Interval	(2-Sided) 90% 57.2 to 113.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Daunorubicinol Dose-normalized Plasma: Cmax
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	72
Geometric Mean (95% Confidence Interval) [(ug/ml)/(mg/m2)]	3.5770	3.3640

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	106.3
	Confidence Interval	(2-Sided) 90% 87.6 to 129.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	10	12
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	10.315	8.1146

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	127.1
	Confidence Interval	(2-Sided) 90% 84.2 to 191.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	10	12
Geometric Mean (95% Confidence Interval) [(h*ug/ml)/(mg/m2)]	34.067	30.820

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	110.5
	Confidence Interval	(2-Sided) 90% 83.9 to 145.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	10	12
Geometric Mean (95% Confidence Interval) [(ug/ml)/(mg/m2)]	11.141	3.8905

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	286.4
	Confidence Interval	(2-Sided) 90% 90.1 to 910.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	10	12
Geometric Mean (95% Confidence Interval) [(ug/ml)/(mg/m2)]	4.0200	1.9868

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Other
	Comments	Bioequivalence

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means (%)
	Estimated Value	202.3
	Confidence Interval	(2-Sided) 90% 131.3 to 311.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Number of Platelet Transfusions Per Week Within Cycles
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Median (Standard Deviation) [Platelet transfusions per week]	1.5 (1.18)	1.4 (1.22)

28. Secondary Outcome

Title	Time to Platelet Count Recovery >=20 Gi/L
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	70	68
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7461
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% 0.28 to 2.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Time to Platelet Recovery >=100 Gi/L
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	73
Median (95% Confidence Interval) [Months]	0.69	0.69

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6175
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95% 0.74 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Number of Participants Who Achieved Platelet Count Recovery by Day 21
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	70	68
Number [Count of participants]	4 5.4%	7 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3224
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.5281
	Confidence Interval	(2-Sided) 95% 0.1084 to 2.2086
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Summary of Platelet Counts Over Time
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Baseline	51.5	50.0
C1D1	52.0	48.5
C1D2	43.5	42.0
C1D3	35.5	37.0
C1D4	36.5	29.0
C1D5	33.0	29.0
C1D6	32.0	30.0
C1D7	27.0	27.0
C1D8	24.0	22.0
C1D9	20.5	19.0
C1D14	16.5	18.0
C1D21	39.0	25.0
C1D28	484.5	121.0
C1D35	547.0	181.0
C1D42	304.0
C2D1	31.0	30.5
C2D2	26.0	28.5
C2D3	25.5	29.0
C2D4	32.0	35.5
C2D5	37.0	22.0
C2D6	27.0	33.0
C2D7	24.0	28.5
C2D14	10.5	16.0
C2D21	27.0	38.0
C2D28	68.0	173.0
C2D35	515.0	272.0
C2D42	147.5

32. Secondary Outcome

Title	Maximum Duration (Days) of Platelet Transfusion Independence
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Median (Full Range) [Days]	29.0	29.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6942
	Comments
	Method	Wilcoxon rank-sum test
	Comments

33. Secondary Outcome

Title	Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Number [Percentage of participants]	55 74.3%	53 71.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7397
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.1151
	Confidence Interval	(2-Sided) 95% 0.5585 to 2.2290
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Time to Neutrophil Engraftment
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	73
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0781
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.46
	Confidence Interval	(2-Sided) 95% 0.95 to 6.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	Summary of Absolute Neutrophil Counts (ANC)
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Baseline	0.8	0.5
C1D1	0.8	0.6
C1D2	0.6	0.5
C1D3	0.6	0.4
C1D4	0.4	0.2
C1D5	0.3	0.2
C1D6	0.2	0.1
C1D7	0.1	0.1
C1D8	0.1	0.0
C1D9	0.0	0.0
C1D14	0.0	0.0
C1D21	0.6	0.3
C1D28	4.3	2.7
C1D35	2.2	1.7
C1D42	3.1
C2D1	0.1	0.0
C2D2	0.1	0.2
C2D3	0.2	0.5
C2D4	0.3	0.5
C2D5	0.2	0.1
C2D6	0.1	0.1
C2D7	0.0	0.1
C2D14	0.0	0.0

36. Secondary Outcome

Title	Summary of Hemoglobin
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Baseline	87.6	87.0
C1D1	88.0	86.0
C1D2	88.0	83.0
C1D3	86.0	82.0
C1D4	83.0	81.5
C1D5	84.0	83.0
C1D6	86.0	82.0
C1D7	85.0	83.0
C1D8	85.3	84.0
C1D9	84.5	81.5
C1D14	85.0	84.0
C1D21	88.0	88.0
C1D28	99.0	98.0
C1D35	99.0	94.0
C1D42	98.0
C2D1	94.5	82.5
C2D2	88.5	86.5
C2D3	86.5	80.0
C2D4	89.0	86.5
C2D5	88.0	84.0
C2D6	84.0	85.0
C2D7	84.5	83.0
C2D14	77.5	87.0
C2D21	86.0	91.0
C2D28	89.0	80.0
C2D35	104.0	87.0
C2D42	90.5

37. Secondary Outcome

Title	Incidence of Hemorrhagic Events
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
C1D7 - GRADE 0	58 78.4%	47 63.5%
C1D7 - GRADE 1	9 12.2%	16 21.6%
C1D7 - GRADE 2	5 6.8%	6 8.1%
C1D7 - GRADE 3	1 1.4%	0 0%
C1D14 - GRADE 0	42 56.8%	43 58.1%
C1D14 - GRADE 1	16 21.6%	13 17.6%
C1D14 - GRADE 2	5 6.8%	6 8.1%
C1D14 - GRADE 3	1 1.4%	0 0%
C1D21 - GRADE 0	36 48.6%	43 58.1%
C1D21 - GRADE 1	13 17.6%	7 9.5%
C1D21 - GRADE 2	3 4.1%	1 1.4%
C1D21 - GRADE 3	0 0%	1 1.4%
C1D28 - GRADE 0	31 41.9%	25 33.8%
C1D28 - GRADE 1	4 5.4%	3 4.1%
C1D28 - GRADE 2	2 2.7%	0 0%
C1D28 - GRADE 3	0 0%	0 0%
C1D35 - GRADE 0	12 16.2%	11 14.9%
C1D35 - GRADE 1	2 2.7%	2 2.7%
C1D35 - GRADE 2	0 0%	0 0%
C1D35 - GRADE 3	0 0%	0 0%
C1D42 - GRADE 0	0 0%
C1D42 - GRADE 1	1 1.4%
C1D42 - GRADE 2	0 0%
C1D42 - GRADE 3	0 0%
C2D1 - GRADE 0	8 10.8%	8 10.8%
C2D1 - GRADE 1	1 1.4%	4 5.4%
C2D1 - GRADE 2	1 1.4%	0 0%
C2D1 - GRADE 3	0 0%	0 0%
C2D7 - GRADE 0	9 12.2%	8 10.8%
C2D7 - GRADE 1	0 0%	3 4.1%
C2D7 - GRADE 2	1 1.4%	0 0%
C2D7 - GRADE 3	0 0%	0 0%
C2D14 - GRADE 0	8 10.8%	7 9.5%
C2D14 - GRADE 1	0 0%	3 4.1%
C2D14 - GRADE 2	0 0%	0 0%
C2D14 - GRADE 3	0 0%	0 0%
C2D21 - GRADE 0	7 9.5%	7 9.5%
C2D21 - GRADE 1	1 1.4%	2 2.7%
C2D21 - GRADE 2	0 0%	0 0%
C2D21 - GRADE 3	0 0%	0 0%
C2D28 - GRADE 0	5 6.8%	7 9.5%
C2D28 - GRADE 1	0 0%	1 1.4%
C2D28 - GRADE 2	0 0%	0 0%
C2D28 - GRADE 3	0 0%	0 0%
C2D35 - GRADE 0	3 4.1%	2 2.7%
C2D35 - GRADE 1	0 0%	1 1.4%
C2D35 - GRADE 2	0 0%	0 0%
C2D35 - GRADE 3	0 0%	0 0%
C2D42 - GRADE 0	0 0%
C2D42 - GRADE 1	1 1.4%
C2D42 - GRADE 2	0 0%
C2D42 - GRADE 3	0 0%
Remission visit GRADE 0	56 75.7%	58 78.4%
Remission visit GRADE 1	2 2.7%	4 5.4%
Remission visit GRADE 2	3 4.1%	0 0%
Remission visit GRADE 3	1 1.4%	0 0%

38. Secondary Outcome

Title	Percentage of Participants With Disease Response Rate and Type of Response
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Overall response	70 94.6%	73 98.6%
Complete Remission (CR)	65 87.8%	70 94.6%
Partial Remission (PR)	5 6.8%	3 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7122
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.8749
	Confidence Interval	(2-Sided) 95% 0.4023 to 1.8943
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Overall Survival (OS)
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
Number [Count of participants]	39 52.7%	30 40.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag (ELQ) QD, Placebo QD
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0688
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.54
	Confidence Interval	(2-Sided) 95% 0.96 to 2.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Number of Participants Who Required Medical Resource Utilization
Description	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)

Outcome Measure Data

Analysis Population Description
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/Group Title	Eltrombopag (ELQ) QD	Placebo QD
Arm/Group Description	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.	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.
Measure Participants	74	74
In-patient hospitalizations/ admissions?	3 4.1%	4 5.4%
Diagnostic imaging procedures performed?	3 4.1%	4 5.4%
Health care resources use or emergency visits?	8 10.8%	6 8.1%
Out-patient lab tests performed?	6 8.1%	6 8.1%

Adverse Events

	Eltrombopag (ELQ) QD		Placebo QD
Time Frame	Adverse events and serious adverse events were collected from Day 1 of cycle 1 until last dose of investigational product + 30 days i.e. a maximum of 114 days (42 days for the induction cycle + 42 days for the re-induction cycle + 30 days for the follow-up)
Adverse Event Reporting Description

Arm/Group Title	Eltrombopag (ELQ) QD		Placebo QD
Arm/Group Description	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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/74 (14.9%)		4/71 (5.6%)
Serious Adverse Events
	Eltrombopag (ELQ) QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/74 (32.4%)		14/71 (19.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/74 (1.4%)		0/71 (0%)
Cardiac disorders
Atrial fibrillation	2/74 (2.7%)		0/71 (0%)
Cardiac failure	1/74 (1.4%)		1/71 (1.4%)
Cardiac failure congestive	0/74 (0%)		1/71 (1.4%)
Cardiomyopathy	0/74 (0%)		1/71 (1.4%)
Left ventricular dysfunction	1/74 (1.4%)		0/71 (0%)
Myocardial infarction	1/74 (1.4%)		0/71 (0%)
Congenital, familial and genetic disorders
Hydrocele	1/74 (1.4%)		0/71 (0%)
Gastrointestinal disorders
Abdominal pain	1/74 (1.4%)		0/71 (0%)
Constipation	0/74 (0%)		1/71 (1.4%)
Neutropenic colitis	0/74 (0%)		1/71 (1.4%)
General disorders
Generalised oedema	0/74 (0%)		1/71 (1.4%)
Pyrexia	1/74 (1.4%)		1/71 (1.4%)
Sudden death	0/74 (0%)		1/71 (1.4%)
Infections and infestations
Acinetobacter bacteraemia	0/74 (0%)		1/71 (1.4%)
Appendicitis	1/74 (1.4%)		0/71 (0%)
Bronchitis	1/74 (1.4%)		0/71 (0%)
Catheter site infection	0/74 (0%)		1/71 (1.4%)
Klebsiella sepsis	1/74 (1.4%)		0/71 (0%)
Neutropenic sepsis	0/74 (0%)		1/71 (1.4%)
Perirectal abscess	0/74 (0%)		1/71 (1.4%)
Pneumonia	0/74 (0%)		1/71 (1.4%)
Sepsis	1/74 (1.4%)		2/71 (2.8%)
Septic shock	2/74 (2.7%)		2/71 (2.8%)
Systemic candida	1/74 (1.4%)		0/71 (0%)
Investigations
Alanine aminotransferase increased	0/74 (0%)		1/71 (1.4%)
Blood bilirubin increased	1/74 (1.4%)		0/71 (0%)
Ejection fraction decreased	0/74 (0%)		2/71 (2.8%)
Metabolism and nutrition disorders
Hypernatraemia	0/74 (0%)		1/71 (1.4%)
Pseudohyperkalaemia	1/74 (1.4%)		0/71 (0%)
Nervous system disorders
Cerebral haemorrhage	1/74 (1.4%)		0/71 (0%)
Cerebrovascular accident	1/74 (1.4%)		0/71 (0%)
Cognitive disorder	1/74 (1.4%)		0/71 (0%)
Haemorrhage intracranial	2/74 (2.7%)		0/71 (0%)
Renal and urinary disorders
Acute kidney injury	3/74 (4.1%)		1/71 (1.4%)
Renal failure	1/74 (1.4%)		0/71 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage	1/74 (1.4%)		0/71 (0%)
Pulmonary embolism	1/74 (1.4%)		0/71 (0%)
Pulmonary haemorrhage	1/74 (1.4%)		0/71 (0%)
Respiratory failure	1/74 (1.4%)		0/71 (0%)
Other (Not Including Serious) Adverse Events
	Eltrombopag (ELQ) QD		Placebo QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/74 (95.9%)		66/71 (93%)
Blood and lymphatic system disorders
Anaemia	7/74 (9.5%)		7/71 (9.9%)
Febrile neutropenia	38/74 (51.4%)		42/71 (59.2%)
Neutropenia	5/74 (6.8%)		5/71 (7%)
Thrombocytopenia	4/74 (5.4%)		4/71 (5.6%)
Thrombocytosis	5/74 (6.8%)		0/71 (0%)
Cardiac disorders
Sinus tachycardia	1/74 (1.4%)		4/71 (5.6%)
Gastrointestinal disorders
Abdominal discomfort	2/74 (2.7%)		4/71 (5.6%)
Abdominal distension	2/74 (2.7%)		6/71 (8.5%)
Abdominal pain	18/74 (24.3%)		17/71 (23.9%)
Abdominal pain lower	0/74 (0%)		4/71 (5.6%)
Abdominal pain upper	3/74 (4.1%)		12/71 (16.9%)
Constipation	28/74 (37.8%)		21/71 (29.6%)
Diarrhoea	42/74 (56.8%)		43/71 (60.6%)
Dry mouth	7/74 (9.5%)		2/71 (2.8%)
Dyspepsia	10/74 (13.5%)		9/71 (12.7%)
Gastrooesophageal reflux disease	2/74 (2.7%)		4/71 (5.6%)
Gingival bleeding	6/74 (8.1%)		4/71 (5.6%)
Gingival pain	4/74 (5.4%)		3/71 (4.2%)
Gingival swelling	3/74 (4.1%)		5/71 (7%)
Haemorrhoids	10/74 (13.5%)		9/71 (12.7%)
Lip dry	4/74 (5.4%)		1/71 (1.4%)
Mouth haemorrhage	5/74 (6.8%)		0/71 (0%)
Mouth ulceration	2/74 (2.7%)		4/71 (5.6%)
Nausea	37/74 (50%)		46/71 (64.8%)
Proctalgia	4/74 (5.4%)		10/71 (14.1%)
Stomatitis	19/74 (25.7%)		18/71 (25.4%)
Vomiting	27/74 (36.5%)		27/71 (38%)
General disorders
Asthenia	13/74 (17.6%)		13/71 (18.3%)
Catheter site haemorrhage	4/74 (5.4%)		1/71 (1.4%)
Chest pain	0/74 (0%)		4/71 (5.6%)
Chills	21/74 (28.4%)		14/71 (19.7%)
Fatigue	10/74 (13.5%)		11/71 (15.5%)
Mucosal inflammation	9/74 (12.2%)		9/71 (12.7%)
Oedema	6/74 (8.1%)		6/71 (8.5%)
Oedema peripheral	12/74 (16.2%)		13/71 (18.3%)
Pain	3/74 (4.1%)		6/71 (8.5%)
Pyrexia	25/74 (33.8%)		17/71 (23.9%)
Infections and infestations
Bacteraemia	4/74 (5.4%)		1/71 (1.4%)
Cellulitis	0/74 (0%)		6/71 (8.5%)
Device related infection	6/74 (8.1%)		9/71 (12.7%)
Oral candidiasis	1/74 (1.4%)		6/71 (8.5%)
Pneumonia	8/74 (10.8%)		3/71 (4.2%)
Sepsis	5/74 (6.8%)		3/71 (4.2%)
Injury, poisoning and procedural complications
Procedural pain	5/74 (6.8%)		5/71 (7%)
Transfusion reaction	10/74 (13.5%)		8/71 (11.3%)
Investigations
Alanine aminotransferase increased	8/74 (10.8%)		14/71 (19.7%)
Aspartate aminotransferase increased	5/74 (6.8%)		8/71 (11.3%)
Blood bilirubin increased	6/74 (8.1%)		8/71 (11.3%)
Neutrophil count decreased	4/74 (5.4%)		1/71 (1.4%)
Platelet count decreased	7/74 (9.5%)		4/71 (5.6%)
Serum ferritin increased	6/74 (8.1%)		2/71 (2.8%)
Weight increased	1/74 (1.4%)		5/71 (7%)
White blood cell count decreased	9/74 (12.2%)		5/71 (7%)
Metabolism and nutrition disorders
Decreased appetite	22/74 (29.7%)		27/71 (38%)
Fluid imbalance	12/74 (16.2%)		10/71 (14.1%)
Fluid overload	6/74 (8.1%)		5/71 (7%)
Hyperkalaemia	4/74 (5.4%)		2/71 (2.8%)
Hypoalbuminaemia	6/74 (8.1%)		2/71 (2.8%)
Hypocalcaemia	7/74 (9.5%)		10/71 (14.1%)
Hypokalaemia	20/74 (27%)		27/71 (38%)
Hypomagnesaemia	8/74 (10.8%)		13/71 (18.3%)
Hyponatraemia	4/74 (5.4%)		4/71 (5.6%)
Hypophosphataemia	10/74 (13.5%)		14/71 (19.7%)
Iron overload	6/74 (8.1%)		3/71 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/74 (8.1%)		3/71 (4.2%)
Back pain	4/74 (5.4%)		15/71 (21.1%)
Musculoskeletal pain	4/74 (5.4%)		5/71 (7%)
Pain in extremity	8/74 (10.8%)		8/71 (11.3%)
Nervous system disorders
Dizziness	11/74 (14.9%)		8/71 (11.3%)
Headache	19/74 (25.7%)		20/71 (28.2%)
Psychiatric disorders
Anxiety	10/74 (13.5%)		7/71 (9.9%)
Insomnia	16/74 (21.6%)		23/71 (32.4%)
Renal and urinary disorders
Haematuria	1/74 (1.4%)		4/71 (5.6%)
Urinary hesitation	5/74 (6.8%)		1/71 (1.4%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/74 (1.4%)		5/71 (7%)
Cough	18/74 (24.3%)		18/71 (25.4%)
Dyspnoea	5/74 (6.8%)		11/71 (15.5%)
Epistaxis	18/74 (24.3%)		14/71 (19.7%)
Haemoptysis	7/74 (9.5%)		2/71 (2.8%)
Hiccups	4/74 (5.4%)		4/71 (5.6%)
Hypoxia	4/74 (5.4%)		2/71 (2.8%)
Nasal dryness	3/74 (4.1%)		5/71 (7%)
Oropharyngeal pain	13/74 (17.6%)		13/71 (18.3%)
Pleural effusion	2/74 (2.7%)		5/71 (7%)
Productive cough	8/74 (10.8%)		4/71 (5.6%)
Rhinorrhoea	8/74 (10.8%)		8/71 (11.3%)
Skin and subcutaneous tissue disorders
Alopecia	1/74 (1.4%)		4/71 (5.6%)
Erythema	5/74 (6.8%)		5/71 (7%)
Hyperhidrosis	5/74 (6.8%)		2/71 (2.8%)
Petechiae	12/74 (16.2%)		10/71 (14.1%)
Pruritus	8/74 (10.8%)		8/71 (11.3%)
Rash	22/74 (29.7%)		13/71 (18.3%)
Rash maculo-papular	8/74 (10.8%)		6/71 (8.5%)
Urticaria	4/74 (5.4%)		4/71 (5.6%)
Vascular disorders
Hypertension	6/74 (8.1%)		8/71 (11.3%)
Hypotension	5/74 (6.8%)		6/71 (8.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety

Results Point of Contact

Name/Title	Clinical Disclosure Office
Organization	Novartis Pharmaceuticals
Phone	862-778-8300
Email	novartis.email@novartis.com

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01890746

Other Study ID Numbers:

117146
2013-000642-20

First Posted:

Jul 2, 2013

Last Update Posted:

Sep 11, 2019

Last Verified:

Aug 1, 2019