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A Safety and Efficacy Study of Eltrombopag in Subjects With AML

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ClinicalTrials.gov Identifier: NCT01890746
Recruitment Status : Completed
First Posted : July 2, 2013
Results First Posted : June 14, 2016
Last Update Posted : September 11, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Acute Leukaemia
Interventions Drug: Daunorubicin
Drug: Cytarabine
Drug: Eltrombopag
Drug: Placebo
Enrollment 148
Recruitment Details Participants (Par.) diagnosed with Acute Myelogenous Leukemia (AML) of any subtype (except acute promyelocytic [M3] or acute megakaryocytic leukaemia [M7]) were eligible for the study.
Pre-assignment Details Sufficient number of participants were screened and 148 participants were randomized and entered in to the study. Participants were stratified by antecedent malignant hematologic disorder (yes versus no) and age (18-60 years versus >60 years), before they were randomized to receive study treatments.
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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
Reason Not Completed
Death             39             30
Adverse Event             1             0
Lost to Follow-up             4             1
Physician Decision             3             2
Withdrawal by Subject             5             8
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD Total
Hide 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 Number of Baseline Participants 74 74 148
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 74 participants 74 participants 148 participants
56.7  (12.25) 56.6  (11.58) 56.7  (11.88)
[1]
Measure Analysis Population Description: The Intent-to-Treat (ITT) population comprised all randomized subjects regardless of whether or not study treatment was administered.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 74 participants 148 participants
Female
38
  51.4%
31
  41.9%
69
  46.6%
Male
36
  48.6%
43
  58.1%
79
  53.4%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 74 participants 74 participants 148 participants
African American/African Heritage 1 2 3
Asian - Central/South Asian Heritage 0 1 1
Asian - East Asian Heritage 26 17 43
Asian - South East Asian Heritage 0 1 1
White - Arabic/North African Heritage 5 3 8
White - White/Caucasian/European Heritage 42 50 92
[1]
Measure Analysis Population Description: The Intent-to-Treat (ITT) population comprised all randomized subjects regardless of whether or not study treatment was administered.
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.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all subjects who received at least one dose of investigational product.
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Measure Type: Number
Unit of Measure: Participants
Any AE 72 66
Any SAE 24 14
2.Primary Outcome
Title Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Population who provided Baseline and Day 42 LVEF measurements.
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Mean (Standard Deviation)
Unit of Measure: LVEF percent
chnge from baseline (BL) to end of study Number Analyzed 57 participants 62 participants
-2.5  (7.81) -4.3  (8.54)
change from BL to worse post-BL case Number Analyzed 58 participants 63 participants
-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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Measure Type: Number
Unit of Measure: Participants
Hemoglobin Low, G3 53 46
Leukocytes, G3 10 10
Leukocytes, G4 9 5
Lymphocytes Low, G3 31 26
Lymphocytes Low, G4 35 38
Neutrophils, G4 44 39
Platelets, G3 1 0
Platelets, G4 63 56
4.Primary Outcome
Title Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Measure Type: Number
Unit of Measure: Participants
Alanine Aminotransferase, G3 1 5
Albumin, G3 6 4
Aspartate Aminotransferase, G3 0 1
Bilirubin, G3 1 4
Bilirubin, G4 0 1
Calcium Low, G3 0 1
Creatinine, G3 0 1
Creatinine, G4 1 0
Glucose High, G3 6 3
Glucose High, G4 0 1
Magnesium Low, G3 0 1
Magnesium High, G3 3 0
Phosphate, G3 10 19
Phosphate, G4 1 0
Potassium Low, G3 8 10
Potassium Low, G4 0 2
Potassium High, G3 4 0
Potassium High, G4 1 1
Sodium Low, G3 3 4
Urate, G4 3 0
5.Primary Outcome
Title Number of Participants With Liver Events.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Measure Type: Number
Unit of Measure: Participants
2 6
6.Primary Outcome
Title Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Measure Type: Number
Unit of Measure: Participants
Normal Number Analyzed 59 participants 63 participants
34 33
Abnormal - NCS Number Analyzed 59 participants 63 participants
23 29
Abnormal - CS Number Analyzed 59 participants 63 participants
2 1
7.Primary Outcome
Title Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Population who provided Baseline and post-Baseline assessments.
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Measure Type: Number
Unit of Measure: Participants
Deteriorated 36 36
Improved 0 1
No Change 37 34
8.Primary Outcome
Title Worst-case Change From Baseline in Pulse Rate Values
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 71
Mean (Standard Deviation)
Unit of Measure: Beats/minute
High Number Analyzed 66 participants 67 participants
18.48  (20.616) 17.73  (15.112)
Low Number Analyzed 61 participants 55 participants
-10.36  (14.039) -11.24  (12.123)
9.Primary Outcome
Title Worst-case Post Baseline Change in Blood Pressure Values From Baseline
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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.
Overall Number of Participants Analyzed 74 71
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 71
Mean (Standard Deviation)
Unit of Measure: Degrees Celsius
High Number Analyzed 70 participants 69 participants
0.62  (0.941) 0.77  (0.879)
Low Number Analyzed 47 participants 43 participants
-0.44  (0.628) -0.63  (0.592)
11.Secondary Outcome
Title Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: hour (h)
15.754
(13.969 to 17.766)
13.709
(12.103 to 15.527)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 114.9
Confidence Interval (2-Sided) 90%
99.5 to 132.7
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: hour (h)
22.735
(21.187 to 24.396)
21.603
(20.232 to 23.067)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 105.2
Confidence Interval (2-Sided) 90%
97.1 to 114.0
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Daunorubicin Dose-normalized Plasma: AUC(0-∞)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
8.0807
(7.0672 to 9.2396)
8.7880
(7.3893 to 10.451)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 92.0
Confidence Interval (2-Sided) 90%
76.8 to 110.2
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Daunorubicinol Dose-normalized Plasma: AUC(0-∞)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
63.997
(58.686 to 69.746)
62.835
(58.673 to 67.292)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 101.8
Confidence Interval (2-Sided) 90%
92.9 to 111.7
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Daunorubicin Dose-normalized Plasma: AUC(24-∞)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
0.87496
(0.76202 to 1.0046)
0.72315
(0.62633 to 0.83493)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 121.0
Confidence Interval (2-Sided) 90%
102.5 to 142.8
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Daunorubicinol Dose-normalized Plasma: AUC(24-∞)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
24.537
(22.052 to 27.301)
23.039
(21.169 to 25.074)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 106.5
Confidence Interval (2-Sided) 90%
95.0 to 119.4
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Daunorubicin Dose-normalized Plasma: AUC(0-t)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
7.9523
(6.9485 to 9.1012)
8.6723
(7.2855 to 10.323)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 91.7
Confidence Interval (2-Sided) 90%
76.5 to 110.0
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Daunorubicinol Dose-normalized Plasma: AUC(0-t)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
62.463
(57.268 to 68.129)
61.608
(57.500 to 66.009)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 101.4
Confidence Interval (2-Sided) 90%
92.4 to 111.2
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Daunorubicin Dose-normalized Plasma: AUC(24-t)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
0.76524
(0.65947 to 0.88797)
0.59660
(0.48882 to 0.72813)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 120.0
Confidence Interval (2-Sided) 90%
100.7 to 142.6
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Daunorubicinol Dose-normalized Plasma: AUC(24-t)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (90% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
22.963
(20.557 to 25.651)
21.821
(20.020 to 23.783)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 105.2
Confidence Interval (2-Sided) 90%
93.6 to 118.3
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Daunorubicin Dose-normalized Plasma: Cmax
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (ug/ml)/(mg/m2)
5.1527
(3.9561 to 6.7114)
6.4113
(4.6773 to 8.7882)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 80.4
Confidence Interval (2-Sided) 90%
57.2 to 113.0
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Daunorubicinol Dose-normalized Plasma: Cmax
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: (ug/ml)/(mg/m2)
3.5770
(3.0433 to 4.2044)
3.3640
(2.8433 to 3.9799)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 106.3
Confidence Interval (2-Sided) 90%
87.6 to 129.0
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 10 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
10.315
(6.7932 to 15.662)
8.1146
(6.0221 to 10.934)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 127.1
Confidence Interval (2-Sided) 90%
84.2 to 191.9
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 10 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: (h*ug/ml)/(mg/m2)
34.067
(26.479 to 43.829)
30.820
(24.148 to 39.335)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 110.5
Confidence Interval (2-Sided) 90%
83.9 to 145.7
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 10 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: (ug/ml)/(mg/m2)
11.141
(4.3653 to 28.432)
3.8905
(1.2805 to 11.820)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 286.4
Confidence Interval (2-Sided) 90%
90.1 to 910.7
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 10 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: (ug/ml)/(mg/m2)
4.0200
(2.5302 to 6.3870)
1.9868
(1.4247 to 2.7708)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Other
Comments Bioequivalence
Method of Estimation Estimation Parameter Ratio of geometric means (%)
Estimated Value 202.3
Confidence Interval (2-Sided) 90%
131.3 to 311.8
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Number of Platelet Transfusions Per Week Within Cycles
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Median (Standard Deviation)
Unit of Measure: Platelet transfusions per week
1.5  (1.18) 1.4  (1.22)
28.Secondary Outcome
Title Time to Platelet Count Recovery >=20 Gi/L
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 70 68
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
N/A = Not enough participants achieved platelet recovery >= 20 Gi/L
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7461
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.28 to 2.48
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Time to Platelet Recovery >=100 Gi/L
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 73
Median (95% Confidence Interval)
Unit of Measure: Months
0.69
(0.69 to 0.76)
0.69
(0.69 to 0.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6175
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.74 to 1.63
Estimation Comments [Not Specified]
30.Secondary Outcome
Title Number of Participants Who Achieved Platelet Count Recovery by Day 21
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 70 68
Measure Type: Number
Unit of Measure: Count of participants
4 7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3224
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.5281
Confidence Interval (2-Sided) 95%
0.1084 to 2.2086
Estimation Comments [Not Specified]
31.Secondary Outcome
Title Summary of Platelet Counts Over Time
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Median (Full Range)
Unit of Measure: Gi/L
Baseline Number Analyzed 74 participants 74 participants
51.5
(5 to 241)
50.0
(9 to 232)
C1D1 Number Analyzed 59 participants 66 participants
52.0
(5 to 241)
48.5
(9 to 232)
C1D2 Number Analyzed 74 participants 74 participants
43.5
(4 to 237)
42.0
(5 to 368)
C1D3 Number Analyzed 72 participants 72 participants
35.5
(4 to 226)
37.0
(7 to 220)
C1D4 Number Analyzed 74 participants 69 participants
36.5
(3 to 227)
29.0
(5 to 146)
C1D5 Number Analyzed 73 participants 71 participants
33.0
(3 to 201)
29.0
(5 to 146)
C1D6 Number Analyzed 73 participants 69 participants
32.0
(4 to 164)
30.0
(6 to 125)
C1D7 Number Analyzed 73 participants 70 participants
27.0
(3 to 123)
27.0
(4 to 102)
C1D8 Number Analyzed 73 participants 69 participants
24.0
(2 to 99)
22.0
(4 to 80)
C1D9 Number Analyzed 72 participants 69 participants
20.5
(1 to 109)
19.0
(5 to 59)
C1D14 Number Analyzed 68 participants 68 participants
16.5
(0 to 70)
18.0
(1 to 81)
C1D21 Number Analyzed 51 participants 55 participants
39.0
(5 to 325)
25.0
(2 to 232)
C1D28 Number Analyzed 36 participants 29 participants
484.5
(14 to 1590)
121.0
(7 to 539)
C1D35 Number Analyzed 14 participants 14 participants
547.0
(15 to 1493)
181.0
(10 to 424)
C1D42 Number Analyzed 0 participants 1 participants
304.0
(304 to 304)
C2D1 Number Analyzed 10 participants 12 participants
31.0
(12 to 1059)
30.5
(10 to 432)
C2D2 Number Analyzed 9 participants 12 participants
26.0
(3 to 831)
28.5
(8 to 400)
C2D3 Number Analyzed 10 participants 12 participants
25.5
(0 to 730)
29.0
(8 to 437)
C2D4 Number Analyzed 9 participants 12 participants
32.0
(2 to 678)
35.5
(11 to 454)
C2D5 Number Analyzed 10 participants 11 participants
37.0
(9 to 516)
22.0
(12 to 476)
C2D6 Number Analyzed 10 participants 12 participants
27.0
(4 to 430)
33.0
(7 to 533)
C2D7 Number Analyzed 7 participants 12 participants
24.0
(6 to 295)
28.5
(12 to 390)
C2D14 Number Analyzed 8 participants 11 participants
10.5
(3 to 31)
16.0
(6 to 66)
C2D21 Number Analyzed 8 participants 11 participants
27.0
(9 to 86)
38.0
(8 to 141)
C2D28 Number Analyzed 5 participants 6 participants
68.0
(48 to 333)
173.0
(32 to 479)
C2D35 Number Analyzed 2 participants 3 participants
515.0
(412 to 618)
272.0
(26 to 329)
C2D42 Number Analyzed 0 participants 2 participants
147.5
(45 to 250)
32.Secondary Outcome
Title Maximum Duration (Days) of Platelet Transfusion Independence
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Median (Full Range)
Unit of Measure: Days
29.0
(2 to 57)
29.5
(2 to 77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6942
Comments [Not Specified]
Method Wilcoxon rank-sum test
Comments [Not Specified]
33.Secondary Outcome
Title Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Measure Type: Number
Unit of Measure: Percentage of participants
55 53
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7397
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.1151
Confidence Interval (2-Sided) 95%
0.5585 to 2.2290
Estimation Comments [Not Specified]
34.Secondary Outcome
Title Time to Neutrophil Engraftment
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 73
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
N/A = Not enough participants achieved ANC>= 0.5 Gi/L
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0781
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.46
Confidence Interval (2-Sided) 95%
0.95 to 6.38
Estimation Comments [Not Specified]
35.Secondary Outcome
Title Summary of Absolute Neutrophil Counts (ANC)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Median (Full Range)
Unit of Measure: Gi/L
Baseline Number Analyzed 71 participants 72 participants
0.8
(0 to 37)
0.5
(0 to 50)
C1D1 Number Analyzed 55 participants 63 participants
0.8
(0 to 37)
0.6
(0 to 50)
C1D2 Number Analyzed 70 participants 72 participants
0.6
(0 to 41)
0.5
(0 to 41)
C1D3 Number Analyzed 66 participants 70 participants
0.6
(0 to 59)
0.4
(0 to 26)
C1D4 Number Analyzed 70 participants 64 participants
0.4
(0 to 35)
0.2
(0 to 17)
C1D5 Number Analyzed 70 participants 63 participants
0.3
(0 to 21)
0.2
(0 to 2)
C1D6 Number Analyzed 68 participants 63 participants
0.2
(0 to 35)
0.1
(0 to 1)
C1D7 Number Analyzed 69 participants 62 participants
0.1
(0 to 29)
0.1
(0 to 1)
C1D8 Number Analyzed 66 participants 58 participants
0.1
(0 to 21)
0.0
(0 to 1)
C1D9 Number Analyzed 66 participants 59 participants
0.0
(0 to 7)
0.0
(0 to 1)
C1D14 Number Analyzed 61 participants 56 participants
0.0
(0 to 1)
0.0
(0 to 0)
C1D21 Number Analyzed 52 participants 51 participants
0.6
(0 to 18)
0.3
(0 to 7)
C1D28 Number Analyzed 37 participants 29 participants
4.3
(0 to 47)
2.7
(0 to 25)
C1D35 Number Analyzed 14 participants 14 participants
2.2
(0 to 56)
1.7
(0 to 12)
C1D42 Number Analyzed 0 participants 1 participants
3.1
(3.1 to 3.1)
C2D1 Number Analyzed 10 participants 9 participants
0.1
(0 to 7)
0.0
(0 to 5)
C2D2 Number Analyzed 10 participants 9 participants
0.1
(0 to 3)
0.2
(0 to 4)
C2D3 Number Analyzed 9 participants 8 participants
0.2
(0 to 5)
0.5
(0 to 4)
C2D4 Number Analyzed 9 participants 9 participants
0.3
(0 to 3)
0.5
(0 to 2)
C2D5 Number Analyzed 10 participants 10 participants
0.2
(0 to 2)
0.1
(0 to 3)
C2D6 Number Analyzed 10 participants 10 participants
0.1
(0 to 1)
0.1
(0 to 3)
C2D7 Number Analyzed 9 participants 8 participants
0.0
(0 to 1)
0.1
(0 to 2)
C2D14 Number Analyzed 7 participants 8 participants
0.0
(0 to 0)
0.0
(0 to 0)
36.Secondary Outcome
Title Summary of Hemoglobin
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Median (Full Range)
Unit of Measure: g/L
Baseline Number Analyzed 74 participants 74 participants
87.6
(63 to 123)
87.0
(67 to 121)
C1D1 Number Analyzed 60 participants 66 participants
88.0
(67 to 123)
86.0
(67 to 121)
C1D2 Number Analyzed 74 participants 74 participants
88.0
(58 to 124)
83.0
(62 to 130)
C1D3 Number Analyzed 74 participants 72 participants
86.0
(52 to 108)
82.0
(59 to 130)
C1D4 Number Analyzed 74 participants 70 participants
83.0
(60 to 105)
81.5
(46 to 120)
C1D5 Number Analyzed 74 participants 71 participants
84.0
(60 to 114)
83.0
(50 to 126)
C1D6 Number Analyzed 74 participants 70 participants
86.0
(67 to 118)
82.0
(52 to 119)
C1D7 Number Analyzed 74 participants 71 participants
85.0
(58 to 116)
83.0
(57 to 110)
C1D8 Number Analyzed 74 participants 70 participants
85.3
(65 to 118)
84.0
(57 to 108)
C1D9 Number Analyzed 74 participants 70 participants
84.5
(64 to 114)
81.5
(62 to 109)
C1D14 Number Analyzed 68 participants 68 participants
85.0
(60 to 123)
84.0
(59 to 109)
C1D21 Number Analyzed 52 participants 55 participants
88.0
(77 to 117)
88.0
(72 to 116)
C1D28 Number Analyzed 37 participants 29 participants
99.0
(78 to 138)
98.0
(79 to 125)
C1D35 Number Analyzed 14 participants 14 participants
99.0
(81 to 131)
94.0
(74 to 130)
C1D42 Number Analyzed 0 participants 1 participants
98.0
(98 to 98)
C2D1 Number Analyzed 10 participants 12 participants
94.5
(76 to 124)
82.5
(72 to 111)
C2D2 Number Analyzed 10 participants 12 participants
88.5
(72 to 112)
86.5
(69 to 104)
C2D3 Number Analyzed 10 participants 12 participants
86.5
(65 to 110)
80.0
(68 to 97)
C2D4 Number Analyzed 10 participants 12 participants
89.0
(72 to 106)
86.5
(74 to 109)
C2D5 Number Analyzed 10 participants 12 participants
88.0
(67 to 101)
84.0
(72 to 93)
C2D6 Number Analyzed 10 participants 12 participants
84.0
(68 to 102)
85.0
(70 to 96)
C2D7 Number Analyzed 10 participants 12 participants
84.5
(66 to 99)
83.0
(57 to 97)
C2D14 Number Analyzed 11 participants 8 participants
77.5
(66 to 101)
87.0
(79 to 96)
C2D21 Number Analyzed 11 participants 8 participants
86.0
(43 to 99)
91.0
(74 to 110)
C2D28 Number Analyzed 7 participants 5 participants
89.0
(80 to 92)
80.0
(72 to 114)
C2D35 Number Analyzed 3 participants 2 participants
104.0
(101 to 107)
87.0
(85 to 119)
C2D42 Number Analyzed 0 participants 2 participants
90.5
(86 to 95)
37.Secondary Outcome
Title Incidence of Hemorrhagic Events
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Measure Type: Number
Unit of Measure: Participants
C1D7 - GRADE 0 Number Analyzed 73 participants 69 participants
58 47
C1D7 - GRADE 1 Number Analyzed 73 participants 69 participants
9 16
C1D7 - GRADE 2 Number Analyzed 73 participants 69 participants
5 6
C1D7 - GRADE 3 Number Analyzed 73 participants 69 participants
1 0
C1D14 - GRADE 0 Number Analyzed 68 participants 65 participants
42 43
C1D14 - GRADE 1 Number Analyzed 68 participants 65 participants
16 13
C1D14 - GRADE 2 Number Analyzed 68 participants 65 participants
5 6
C1D14 - GRADE 3 Number Analyzed 68 participants 65 participants
1 0
C1D21 - GRADE 0 Number Analyzed 52 participants 52 participants
36 43
C1D21 - GRADE 1 Number Analyzed 52 participants 52 participants
13 7
C1D21 - GRADE 2 Number Analyzed 52 participants 52 participants
3 1
C1D21 - GRADE 3 Number Analyzed 52 participants 52 participants
0 1
C1D28 - GRADE 0 Number Analyzed 37 participants 28 participants
31 25
C1D28 - GRADE 1 Number Analyzed 37 participants 28 participants
4 3
C1D28 - GRADE 2 Number Analyzed 37 participants 28 participants
2 0
C1D28 - GRADE 3 Number Analyzed 37 participants 28 participants
0 0
C1D35 - GRADE 0 Number Analyzed 14 participants 13 participants
12 11
C1D35 - GRADE 1 Number Analyzed 14 participants 13 participants
2 2
C1D35 - GRADE 2 Number Analyzed 14 participants 13 participants
0 0
C1D35 - GRADE 3 Number Analyzed 14 participants 13 participants
0 0
C1D42 - GRADE 0 Number Analyzed 0 participants 1 participants
0
C1D42 - GRADE 1 Number Analyzed 0 participants 1 participants
1
C1D42 - GRADE 2 Number Analyzed 0 participants 1 participants
0
C1D42 - GRADE 3 Number Analyzed 0 participants 1 participants
0
C2D1 - GRADE 0 Number Analyzed 10 participants 12 participants
8 8
C2D1 - GRADE 1 Number Analyzed 10 participants 12 participants
1 4
C2D1 - GRADE 2 Number Analyzed 10 participants 12 participants
1 0
C2D1 - GRADE 3 Number Analyzed 10 participants 12 participants
0 0
C2D7 - GRADE 0 Number Analyzed 10 participants 11 participants
9 8
C2D7 - GRADE 1 Number Analyzed 10 participants 11 participants
0 3
C2D7 - GRADE 2 Number Analyzed 10 participants 11 participants
1 0
C2D7 - GRADE 3 Number Analyzed 10 participants 11 participants
0 0
C2D14 - GRADE 0 Number Analyzed 8 participants 10 participants
8 7
C2D14 - GRADE 1 Number Analyzed 8 participants 10 participants
0 3
C2D14 - GRADE 2 Number Analyzed 8 participants 10 participants
0 0
C2D14 - GRADE 3 Number Analyzed 8 participants 10 participants
0 0
C2D21 - GRADE 0 Number Analyzed 8 participants 9 participants
7 7
C2D21 - GRADE 1 Number Analyzed 8 participants 9 participants
1 2
C2D21 - GRADE 2 Number Analyzed 8 participants 9 participants
0 0
C2D21 - GRADE 3 Number Analyzed 8 participants 9 participants
0 0
C2D28 - GRADE 0 Number Analyzed 5 participants 8 participants
5 7
C2D28 - GRADE 1 Number Analyzed 5 participants 8 participants
0 1
C2D28 - GRADE 2 Number Analyzed 5 participants 8 participants
0 0
C2D28 - GRADE 3 Number Analyzed 5 participants 8 participants
0 0
C2D35 - GRADE 0 Number Analyzed 3 participants 3 participants
3 2
C2D35 - GRADE 1 Number Analyzed 3 participants 3 participants
0 1
C2D35 - GRADE 2 Number Analyzed 3 participants 3 participants
0 0
C2D35 - GRADE 3 Number Analyzed 3 participants 3 participants
0 0
C2D42 - GRADE 0 Number Analyzed 0 participants 1 participants
0
C2D42 - GRADE 1 Number Analyzed 0 participants 1 participants
1
C2D42 - GRADE 2 Number Analyzed 0 participants 1 participants
0
C2D42 - GRADE 3 Number Analyzed 0 participants 1 participants
0
Remission visit GRADE 0 Number Analyzed 62 participants 62 participants
56 58
Remission visit GRADE 1 Number Analyzed 62 participants 62 participants
2 4
Remission visit GRADE 2 Number Analyzed 62 participants 62 participants
3 0
Remission visit GRADE 3 Number Analyzed 62 participants 62 participants
1 0
38.Secondary Outcome
Title Percentage of Participants With Disease Response Rate and Type of Response
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Measure Type: Number
Unit of Measure: Percentage of participants
Overall response 70 73
Complete Remission (CR) 65 70
Partial Remission (PR) 5 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7122
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8749
Confidence Interval (2-Sided) 95%
0.4023 to 1.8943
Estimation Comments [Not Specified]
39.Secondary Outcome
Title Overall Survival (OS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Measure Type: Number
Unit of Measure: Count of participants
39 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eltrombopag (ELQ) QD, Placebo QD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0688
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.54
Confidence Interval (2-Sided) 95%
0.96 to 2.47
Estimation Comments [Not Specified]
40.Secondary Outcome
Title Number of Participants Who Required Medical Resource Utilization
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 74 74
Measure Type: Number
Unit of Measure: Count of participants
In-patient hospitalizations/ admissions? 3 4
Diagnostic imaging procedures performed? 3 4
Health care resources use or emergency visits? 8 6
Out-patient lab tests performed? 6 6
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 [Not Specified]
 
Arm/Group Title Eltrombopag (ELQ) QD Placebo QD
Hide 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
Eltrombopag (ELQ) QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%)
Total   11/74 (14.86%)   4/71 (5.63%) 
Show Serious Adverse Events Hide Serious Adverse Events
Eltrombopag (ELQ) QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%)
Total   24/74 (32.43%)   14/71 (19.72%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  1/74 (1.35%)  0/71 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  2/74 (2.70%)  0/71 (0.00%) 
Cardiac failure  1  1/74 (1.35%)  1/71 (1.41%) 
Cardiac failure congestive  1  0/74 (0.00%)  1/71 (1.41%) 
Cardiomyopathy  1  0/74 (0.00%)  1/71 (1.41%) 
Left ventricular dysfunction  1  1/74 (1.35%)  0/71 (0.00%) 
Myocardial infarction  1  1/74 (1.35%)  0/71 (0.00%) 
Congenital, familial and genetic disorders     
Hydrocele  1  1/74 (1.35%)  0/71 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/74 (1.35%)  0/71 (0.00%) 
Constipation  1  0/74 (0.00%)  1/71 (1.41%) 
Neutropenic colitis  1  0/74 (0.00%)  1/71 (1.41%) 
General disorders     
Generalised oedema  1  0/74 (0.00%)  1/71 (1.41%) 
Pyrexia  1  1/74 (1.35%)  1/71 (1.41%) 
Sudden death  1  0/74 (0.00%)  1/71 (1.41%) 
Infections and infestations     
Acinetobacter bacteraemia  1  0/74 (0.00%)  1/71 (1.41%) 
Appendicitis  1  1/74 (1.35%)  0/71 (0.00%) 
Bronchitis  1  1/74 (1.35%)  0/71 (0.00%) 
Catheter site infection  1  0/74 (0.00%)  1/71 (1.41%) 
Klebsiella sepsis  1  1/74 (1.35%)  0/71 (0.00%) 
Neutropenic sepsis  1  0/74 (0.00%)  1/71 (1.41%) 
Perirectal abscess  1  0/74 (0.00%)  1/71 (1.41%) 
Pneumonia  1  0/74 (0.00%)  1/71 (1.41%) 
Sepsis  1  1/74 (1.35%)  2/71 (2.82%) 
Septic shock  1  2/74 (2.70%)  2/71 (2.82%) 
Systemic candida  1  1/74 (1.35%)  0/71 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  0/74 (0.00%)  1/71 (1.41%) 
Blood bilirubin increased  1  1/74 (1.35%)  0/71 (0.00%) 
Ejection fraction decreased  1  0/74 (0.00%)  2/71 (2.82%) 
Metabolism and nutrition disorders     
Hypernatraemia  1  0/74 (0.00%)  1/71 (1.41%) 
Pseudohyperkalaemia  1  1/74 (1.35%)  0/71 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage  1  1/74 (1.35%)  0/71 (0.00%) 
Cerebrovascular accident  1  1/74 (1.35%)  0/71 (0.00%) 
Cognitive disorder  1  1/74 (1.35%)  0/71 (0.00%) 
Haemorrhage intracranial  1  2/74 (2.70%)  0/71 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  3/74 (4.05%)  1/71 (1.41%) 
Renal failure  1  1/74 (1.35%)  0/71 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary alveolar haemorrhage  1  1/74 (1.35%)  0/71 (0.00%) 
Pulmonary embolism  1  1/74 (1.35%)  0/71 (0.00%) 
Pulmonary haemorrhage  1  1/74 (1.35%)  0/71 (0.00%) 
Respiratory failure  1  1/74 (1.35%)  0/71 (0.00%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Eltrombopag (ELQ) QD Placebo QD
Affected / at Risk (%) Affected / at Risk (%)
Total   71/74 (95.95%)   66/71 (92.96%) 
Blood and lymphatic system disorders     
Anaemia  1  7/74 (9.46%)  7/71 (9.86%) 
Febrile neutropenia  1  38/74 (51.35%)  42/71 (59.15%) 
Neutropenia  1  5/74 (6.76%)  5/71 (7.04%) 
Thrombocytopenia  1  4/74 (5.41%)  4/71 (5.63%) 
Thrombocytosis  1  5/74 (6.76%)  0/71 (0.00%) 
Cardiac disorders     
Sinus tachycardia  1  1/74 (1.35%)  4/71 (5.63%) 
Gastrointestinal disorders     
Abdominal discomfort  1  2/74 (2.70%)  4/71 (5.63%) 
Abdominal distension  1  2/74 (2.70%)  6/71 (8.45%) 
Abdominal pain  1  18/74 (24.32%)  17/71 (23.94%) 
Abdominal pain lower  1  0/74 (0.00%)  4/71 (5.63%) 
Abdominal pain upper  1  3/74 (4.05%)  12/71 (16.90%) 
Constipation  1  28/74 (37.84%)  21/71 (29.58%) 
Diarrhoea  1  42/74 (56.76%)  43/71 (60.56%) 
Dry mouth  1  7/74 (9.46%)  2/71 (2.82%) 
Dyspepsia  1  10/74 (13.51%)  9/71 (12.68%) 
Gastrooesophageal reflux disease  1  2/74 (2.70%)  4/71 (5.63%) 
Gingival bleeding  1  6/74 (8.11%)  4/71 (5.63%) 
Gingival pain  1  4/74 (5.41%)  3/71 (4.23%) 
Gingival swelling  1  3/74 (4.05%)  5/71 (7.04%) 
Haemorrhoids  1  10/74 (13.51%)  9/71 (12.68%) 
Lip dry  1  4/74 (5.41%)  1/71 (1.41%) 
Mouth haemorrhage  1  5/74 (6.76%)  0/71 (0.00%) 
Mouth ulceration  1  2/74 (2.70%)  4/71 (5.63%) 
Nausea  1  37/74 (50.00%)  46/71 (64.79%) 
Proctalgia  1  4/74 (5.41%)  10/71 (14.08%) 
Stomatitis  1  19/74 (25.68%)  18/71 (25.35%) 
Vomiting  1  27/74 (36.49%)  27/71 (38.03%) 
General disorders     
Asthenia  1  13/74 (17.57%)  13/71 (18.31%) 
Catheter site haemorrhage  1  4/74 (5.41%)  1/71 (1.41%) 
Chest pain  1  0/74 (0.00%)  4/71 (5.63%) 
Chills  1  21/74 (28.38%)  14/71 (19.72%) 
Fatigue  1  10/74 (13.51%)  11/71 (15.49%) 
Mucosal inflammation  1  9/74 (12.16%)  9/71 (12.68%) 
Oedema  1  6/74 (8.11%)  6/71 (8.45%) 
Oedema peripheral  1  12/74 (16.22%)  13/71 (18.31%) 
Pain  1  3/74 (4.05%)  6/71 (8.45%) 
Pyrexia  1  25/74 (33.78%)  17/71 (23.94%) 
Infections and infestations     
Bacteraemia  1  4/74 (5.41%)  1/71 (1.41%) 
Cellulitis  1  0/74 (0.00%)  6/71 (8.45%) 
Device related infection  1  6/74 (8.11%)  9/71 (12.68%) 
Oral candidiasis  1  1/74 (1.35%)  6/71 (8.45%) 
Pneumonia  1  8/74 (10.81%)  3/71 (4.23%) 
Sepsis  1  5/74 (6.76%)  3/71 (4.23%) 
Injury, poisoning and procedural complications     
Procedural pain  1  5/74 (6.76%)  5/71 (7.04%) 
Transfusion reaction  1  10/74 (13.51%)  8/71 (11.27%) 
Investigations     
Alanine aminotransferase increased  1  8/74 (10.81%)  14/71 (19.72%) 
Aspartate aminotransferase increased  1  5/74 (6.76%)  8/71 (11.27%) 
Blood bilirubin increased  1  6/74 (8.11%)  8/71 (11.27%) 
Neutrophil count decreased  1  4/74 (5.41%)  1/71 (1.41%) 
Platelet count decreased  1  7/74 (9.46%)  4/71 (5.63%) 
Serum ferritin increased  1  6/74 (8.11%)  2/71 (2.82%) 
Weight increased  1  1/74 (1.35%)  5/71 (7.04%) 
White blood cell count decreased  1  9/74 (12.16%)  5/71 (7.04%) 
Metabolism and nutrition disorders     
Decreased appetite  1  22/74 (29.73%)  27/71 (38.03%) 
Fluid imbalance  1  12/74 (16.22%)  10/71 (14.08%) 
Fluid overload  1  6/74 (8.11%)  5/71 (7.04%) 
Hyperkalaemia  1  4/74 (5.41%)  2/71 (2.82%) 
Hypoalbuminaemia  1  6/74 (8.11%)  2/71 (2.82%) 
Hypocalcaemia  1  7/74 (9.46%)  10/71 (14.08%) 
Hypokalaemia  1  20/74 (27.03%)  27/71 (38.03%) 
Hypomagnesaemia  1  8/74 (10.81%)  13/71 (18.31%) 
Hyponatraemia  1  4/74 (5.41%)  4/71 (5.63%) 
Hypophosphataemia  1  10/74 (13.51%)  14/71 (19.72%) 
Iron overload  1  6/74 (8.11%)  3/71 (4.23%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/74 (8.11%)  3/71 (4.23%) 
Back pain  1  4/74 (5.41%)  15/71 (21.13%) 
Musculoskeletal pain  1  4/74 (5.41%)  5/71 (7.04%) 
Pain in extremity  1  8/74 (10.81%)  8/71 (11.27%) 
Nervous system disorders     
Dizziness  1  11/74 (14.86%)  8/71 (11.27%) 
Headache  1  19/74 (25.68%)  20/71 (28.17%) 
Psychiatric disorders     
Anxiety  1  10/74 (13.51%)  7/71 (9.86%) 
Insomnia  1  16/74 (21.62%)  23/71 (32.39%) 
Renal and urinary disorders     
Haematuria  1  1/74 (1.35%)  4/71 (5.63%) 
Urinary hesitation  1  5/74 (6.76%)  1/71 (1.41%) 
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  1/74 (1.35%)  5/71 (7.04%) 
Cough  1  18/74 (24.32%)  18/71 (25.35%) 
Dyspnoea  1  5/74 (6.76%)  11/71 (15.49%) 
Epistaxis  1  18/74 (24.32%)  14/71 (19.72%) 
Haemoptysis  1  7/74 (9.46%)  2/71 (2.82%) 
Hiccups  1  4/74 (5.41%)  4/71 (5.63%) 
Hypoxia  1  4/74 (5.41%)  2/71 (2.82%) 
Nasal dryness  1  3/74 (4.05%)  5/71 (7.04%) 
Oropharyngeal pain  1  13/74 (17.57%)  13/71 (18.31%) 
Pleural effusion  1  2/74 (2.70%)  5/71 (7.04%) 
Productive cough  1  8/74 (10.81%)  4/71 (5.63%) 
Rhinorrhoea  1  8/74 (10.81%)  8/71 (11.27%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  1/74 (1.35%)  4/71 (5.63%) 
Erythema  1  5/74 (6.76%)  5/71 (7.04%) 
Hyperhidrosis  1  5/74 (6.76%)  2/71 (2.82%) 
Petechiae  1  12/74 (16.22%)  10/71 (14.08%) 
Pruritus  1  8/74 (10.81%)  8/71 (11.27%) 
Rash  1  22/74 (29.73%)  13/71 (18.31%) 
Rash maculo-papular  1  8/74 (10.81%)  6/71 (8.45%) 
Urticaria  1  4/74 (5.41%)  4/71 (5.63%) 
Vascular disorders     
Hypertension  1  6/74 (8.11%)  8/71 (11.27%) 
Hypotension  1  5/74 (6.76%)  6/71 (8.45%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01890746     History of Changes
Other Study ID Numbers: 117146
2013-000642-20 ( EudraCT Number )
First Submitted: June 27, 2013
First Posted: July 2, 2013
Results First Submitted: March 7, 2016
Results First Posted: June 14, 2016
Last Update Posted: September 11, 2019