Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01890746 | A Safety and Efficacy Study of Eltrombopag in Subjects With AML | PHASE2 | COMPLETED | 148 | — | — | Sep 5, 2013 | Jan 25, 2017 | Sep 11, 2019 | 42 | United States, Australia +8 |
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.
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.
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.
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.
The number of participants with liver enzyme (ALT, AST, ALP, Total bilirubin) abnormalities while receiving study treatment in each arm are presented.
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.
The number of participants with worst case post-baseline changes (improved, no change, deteriorated) are presented.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Eltrombopag arm | EXPERIMENTAL | Subjects received induction chemotherapy consisting of daunorubicin bolus intravenous (IV) infusion on Days 1-3 + cytarabine continuous IV infusion on Days 1-7 followed by Eltrombopag once daily orally starting on Day 4 of initial induction chemotherapy. If platelet count was not greater than 100 Gi/L after 7 days the dose was increased until a platelet count of at least 200 Gi/L was achieved/until remission was assessed/ maximum of 42 days from the start of the chemotherapy induction. Subjects who were not aplastic after first cycle of induction chemotherapy received second induction chemotherapy with a modified daunorubicin dose on Days 1-3 + cytarabine on Days 1-7. |
| Placebo arm | PLACEBO_COMPARATOR | Subject received induction chemotherapy consisting of daunorubicin bolus IV infusion on Days 1-3 + cytarabine continuous IV infusion on Days 1-7 followed by matching placebo once daily oral dose starting on Day 4 of initial induction chemotherapy. If platelet count was not greater than 100 Gi/L after 7 days the matching placebo was given until a platelet count of at least 200 Gi/L was achieved/ until remission was assessed/ maximum of 42 days from the start of the chemotherapy induction. Subjects who were not aplastic after first cycle of induction chemotherapy received a second induction chemotherapy with a modified daunorubicin dose on Days 1-3 + cytarabine on Days 1-7. |
| Name | Type | Description |
|---|---|---|
| Daunorubicin | DRUG | For subjects between the ages of 18 and 60 years, 90 mg/m2/day by bolus IV injection through a freshly established free-flowing IV line for 10-15 minutes on days 1, 2, and 3. For subjects \> 60 years: daunorubicin dose was adjusted to 60mg /m2. |
| Cytarabine | DRUG | 100 mg/m2/day continuous IV infusion on Days 1 through 7. |
| Eltrombopag | DRUG | 200 mg orally, once daily, beginning on Day 4 of the first cycle of induction. After 7 days, the dose of the Investigational Product (IP) was to be increased to 300 mg if platelet counts were \<100 Gi/L. IP continued until achievement of platelet count of at least 200 Gi/L or assessment of remission of bone marrow status or a maximum of 42 days after initiation of most recent induction. In subjects of East Asian heritage 100 mg orally once daily (a 50% dose reduction) was used and after 7 days, the dose of IP was increased to 150 mg if platelet counts were \<100 Gi/L. |
| Placebo | DRUG | Orally, once daily, beginning on Day 4 of the first cycle of induction. After 7 days, the dose given was matching 300 mg Eltrombopag if platelet counts were \<100 Gi/L. Placebo continued until achievement of platelet count of at least 200 Gi/L or assessment of remission of bone marrow status or a maximum of 42 days after initiation of most recent induction. In subjects of East Asian heritage placebo matching 100 mg Eltrombopag orally once daily was used and after 7 days, the placebo matching 150 mg Eltrombopag was given if platelet counts were \<100 Gi/L. |
Inclusion Criteria * Age \>=18 years * Diagnosed with AML according to the WHO 2008 classification. Note: subjects with secondary AML following Myelodysplastic syndrome or secondary to previous leukemogenic therapy are allowed provided that a record of previous MDS history or leukemogenic therapy h...