Thrombocytopaenia
Conditions
Keywords
acute myeloid leukemia (AML), acute myelogenous leukemia (AML), acute non lymphocytic leukemia (ANLL), myeloproliferative disease (MDS), myelodysplastic syndrome ( secondary acute myeloid leukemia), refractory acute myeloid leukemia
Brief summary
This was a worldwide, three-part (Part 1: open-label, Part 2: randomized, double-blind, Part 3: extension), multi-center study to evaluate the effect of eltrombopag in subjects with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who have thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy. This objective was assessed by a composite primary endpoint that consists of the following: the proportion of ≥Grade 3 hemorrhagic adverse events, or platelet counts \<10 Gi/L, or platelet transfusions. Patients with MDS or AML and Grade 4 thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy were enrolled in the study. No low or intermediate-1 risk MDS subjects were enrolled in the study. Subjects must have had at least one of the following during the 4 weeks prior to enrolment: platelet count \<10 Gi/L, platelet transfusion, or symptomatic hemorrhagic event. Supportive standard of care (SOC), including hydroxyurea, was allowed as indicated by local practice throughout the study. The study had 3 sequential parts. Subjects who were enrolled in Part 1 (open-label) cannot be enrolled in Part 2 of the study (randomized, double-blind); however, subjects who completed the treatment period for Part 1 or Part 2 (8 and 12 weeks, respectively) continued in Part 3 (extension) if the investigator determined that the subject was receiving clinical benefit on treatment.
Interventions
DRUGeltrombopag
100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
DRUGplacebo
100 mg matching placebo daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg matching placebo (150 mg for subjects of East Asian heritage)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
* Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts ≤50%) with thrombocytopenia due to bone marrow insufficiency from the disease or prior treatment. Subjects with transient thrombocytopenia due to active treatment with disease modifying agents or chemotherapy (except for hydroxyurea) are excluded. * Subjects must have Grade 4 thrombocytopenia (platelet counts \<25 Gi/L) due to bone marrow insufficiency (or Grade 4 thrombocytopenia, but platelet count greater than or equal to 25 Gi/L due to platelet transfusion). In addition, subjects must have had at least one of the following during the 4 week screening period: platelet transfusion, or symptomatic bleeding or platelet count \<10 Gi/L. Subjects whose thrombocytopenia below 10 Gi/L is due to causes other than bone marrow insufficiency (e.g., fever, infection, autoimmune disease) are not eligible. * Subjects must have platelet count, bleeding and platelet transfusion data available over a period of at least 4 weeks prior to randomization. * Prior systemic treatment for malignancy, with the exception of hydroxyurea, must have been discontinued prior to entry into the study: at least 4 weeks before Day 1 for the following: chemotherapy, demethylating agents (azacitidine or decitabine), lenalidomide, thalidomide, clofarabine and IL-11(oprelvekin); at least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin. * Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT. * Subjects must be stable and, in the opinion of the investigator, be expected to complete a 12 week treatment period. * ECOG Status 0-2. * Subject must be able to understand and comply with protocol requirements and instructions. * Subject has signed and dated an informed consent form. * Adequate baseline organ function defined by the criteria below: total bilirubin ≤ 1.5xULN except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect (hemolytic) bilirubin in the absence of ALT abnormality), ALT ≤ 3xULN, creatinine ≤ 2.5xULN * Women must be either of non-child bearing potential or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the first dose of study treatment. * In France, a subject eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Exclusion criteria
* Subjects with MDS and an IPSS of low or intermediate-1 risk at screening. * Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML secondary to a myeloproliferative neoplasm. * History of treatment with romiplostim or other TPO-R agonists. * Subjects with a QTc \>480 msec (QTc \>510 msec for subjects with Bundle Branch Block). * Leukocytosis ≥25,000/uL on Day 1 of treatment with study medication. * Subjects with known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator. * Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin \[β-hCG\] pregnancy test) at screening or pre-dose on Day 1. * Current alcohol or drug abuse. * Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication. * Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C). * Subjects infected with Human Immunodeficiency Virus (HIV). * Subjects with liver cirrhosis (as determined by the investigator). * Subjects receiving or planned to receive any prohibited medication. * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidone, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjects' participation. * In France, subjects who have participated in any study using an investigational drug during the previous 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Platelet Response up to Week 8 During Part 1 | From Baseline up to Week 8 during Part 1 | A participant was considered as a responder if he/she met the following response criteria: a Baseline platelet count \<20 Giga cells per liter (Gi/L) and a post-Baseline increased to \>20 Gi/L and at least 2 times the Baseline value; or a Baseline platelet count \>=20 Gi/L and a post-Baseline absolute platelet count increased to \>=50 Gi/L and at least 2 times the Baseline value. The response criteria was evaluated at each visit. Increase in platelet count observed up to 3 days after a platelet transfusion was not considered as a platelet response. The Part 1 Population was comprised of all participants enrolled into Part 1. |
| Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2 | From Week 5 up to Week 12 during Part 2 | A participant was considered to have a CRTE at a given assessment if he/she had platelet counts \<10 Gi/L, or platelet transfusions, or \>=Grade 3 hemorrhagic adverse events. CRTEs during Weeks 5 to 12 were compared between treatments using a generalized linear mixed model. Average of weekly proportion of subjects with CRTE during Week 5 to 12 was estimated for each treatment. Intent to Treat (ITT) Population was comprised of all randomized participants during Part 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Platelet Transfusions | Weeks 5 to 12 | — |
| Hematologic Improvement | Weeks 5 to 12 | Definitions of hematologic improvement for platelets, neutrophils, and hemoglobin were based on modified International Working Group (IWG) consensus criteria. |
| Change in Mean Platelet Count | Baseline to Week 12 | — |
| Maximum Duration of Platelet Transfusion Independence | Weeks 5 to 12 | — |
| Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Weeks 5 to 12 | Occurrence and severity of bleeding, measured using the WHO Bleeding Scale Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross blood loss; Grade 4=debilitating blood loss. |
| Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day 1 to week 8 | — |
| Independent Reviewer Assessed Disease Progression | Up to week 12 | — |
| Median Overall Survival | Up to 13 months | — |
| Summary of Health Outcomes | week 12 | The number of subject with medical resource utilization (MRU) data are reported in this table. MRU included number of emergency room visits, number of home healthcare visits, number of hospitalization days, number of medication or surgery specialist visits, number of procedures inpatient, number of procedures outpatient, number of non-study radiology visits, number of non-study laboratory visits, number of nurse practitioner/physician assistance/nurse visits, number of primary care physician visits, number of telephone consultations. |
| Functional Assessment of Cancer Therapy (FACT) | Change from baseline, up to week 12 | The FACT-Th-18 is the most widely used and accepted tool evaluating health-related quality-of-life outcomes in cancer patients with chronically low platelets (where Th designates thrombocytopenia). The entire FACT-Th-18 was used in this trial, which includes the 18-item thrombocytopenia subscale used to assess the impact of symptoms, signs, and functional consequences of thrombocytopenia in MDS and AML subjects. The FACT-Th-18 is a validated and reliable instrument with known psychometric properties. FACT-ThS is an 18 item questionnaire specific to assessing the impact of symptoms, signs, and functional consequences of Thrombocytopenia. ThS score ranges from 0 to 72 with higher the score, the better the QoL. FACT G total score moves from 0 to 108 where higher the score, the better the HRQL. FACT-Th Total Score is calculated by adding the FACT-ThS and FACT-G score. Total score ranges from 0 to 180 and again, higher the score, the better the HRQL. |
| EQ-5D Utility Score Analysis | Change from baseline, up to week 12 | EuroQoL Five Dimensions Questionnaire (EQ-5D) is a standardized generic preference based health related quality of life instrument. It records how one's health is today and consists of a descriptive system. The Descriptive system is Comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life. EQ-ED is a score. |
| Independent Reviewer-Assessed Best Response | up to week 12 | Participants were evaluated in accordance with the modified International Working Group (Cheson, 2006). CR: Bone marrow blasts \<5%, Hgb ≥11g/dL, Hematologic Improvement - Platelets (Baseline \<20Gi/L: \>20 Gi/L and 2x baseline; Baseline ≥20 Gi/L: ≥50 Gi/L and 2x baseline), Neutrophils ≥1.0 Gi/L, Peripheral blasts 0%. PR: Bone marrow blasts decreased by ≥50% but \>5%, Peripheral blood as in CR. Marrow CR: Bone marrow blasts \<5% and decrease by ≥50%, Note any Hematologic Improvements, Stable disease: Failure to achieve PR, but no evidence of progression for \>8w, Cytogenetic response: Complete: disappearance of chromosomal abnormality; no new abnormalities Partial: ≥50% reduction of chromosomal abnormality. |
| Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day 1 to week 12 | — |
Countries
Argentina, Belgium, Brazil, Canada, Czechia, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Mexico, Netherlands, Poland, Puerto Rico, Russia, South Korea, Spain, Taiwan, Thailand, United States
Participant flow
Recruitment details
Part 1, 17 subjects received open-label eltrombopag. Part 2, 145 subjects were randomized to receive eltrombopag plus SOC (N=98) or placebo plus SOC (N=47). Part 3, 59 subjects from Part 2 entered Part 3. SOC was allowed as needed throughout the study. Subjects could receive disease-modifying therapy as needed.
Pre-assignment details
Participants with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and Grade 4 thrombocytopenia due to bone marrow insufficiency and had at least one of the following: platelet count \<10 Giga cells per liter, platelet transfusion or symptomatic hemorrhagic event during the 4 weeks prior to enrollment, were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks. | 17 |
| Part 2: Placebo Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study. | 47 |
| Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study. | 98 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: Open-label Phase | Adverse Event | 5 | 0 | 0 | 0 |
| Part 1: Open-label Phase | Physician Decision | 1 | 0 | 0 | 0 |
| Part 2; Double-blind Phase | Adverse Event | 0 | 7 | 31 | 0 |
| Part 2; Double-blind Phase | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Part 2; Double-blind Phase | Not treated | 0 | 0 | 1 | 0 |
| Part 2; Double-blind Phase | Physician Decision | 0 | 8 | 17 | 0 |
| Part 2; Double-blind Phase | Protocol Violation | 0 | 0 | 1 | 0 |
| Part 2; Double-blind Phase | Withdrawal by Subject | 0 | 4 | 5 | 0 |
| Part 3: Extension | Adverse Event | 0 | 0 | 0 | 13 |
| Part 3: Extension | Physician Decision | 0 | 0 | 0 | 14 |
| Part 3: Extension | Withdrawal by Subject | 0 | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Part 1: Eltrombopag | Part 2: Placebo | Part 2: Eltrombopag | Total |
|---|---|---|---|---|
| Age, Continuous | 71.5 Years STANDARD_DEVIATION 10.78 | 70.6 Years STANDARD_DEVIATION 10.72 | 72.3 Years STANDARD_DEVIATION 8.94 | 71.8 Years STANDARD_DEVIATION 9.56 |
| Race/Ethnicity, Customized African American/African Heritage | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 3 Participants | 5 Participants | 9 Participants | 17 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 0 Participants | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 14 Participants | 39 Participants | 81 Participants | 134 Participants |
| Sex: Female, Male Female | 7 Participants | 16 Participants | 32 Participants | 55 Participants |
| Sex: Female, Male Male | 10 Participants | 31 Participants | 66 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 17 | 89 / 97 | 44 / 47 | 54 / 59 |
| serious Total, serious adverse events | 9 / 17 | 56 / 97 | 32 / 47 | 39 / 59 |
Outcome results
Primary
Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2
A participant was considered to have a CRTE at a given assessment if he/she had platelet counts \<10 Gi/L, or platelet transfusions, or \>=Grade 3 hemorrhagic adverse events. CRTEs during Weeks 5 to 12 were compared between treatments using a generalized linear mixed model. Average of weekly proportion of subjects with CRTE during Week 5 to 12 was estimated for each treatment. Intent to Treat (ITT) Population was comprised of all randomized participants during Part 2.
Time frame: From Week 5 up to Week 12 during Part 2
Population: Part 2 Population (Intent-To-Treat (ITT) Population: all randomized subjects in part 2)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: Eltrombopag | Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2 | 69 percentages of participants |
| Part 2: Eltrombopag | Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2 | 54 percentages of participants |
p-value: 0.031595% CI: [0.047, 0.868]Generalized Linear Mixed Models
Primary
Number of Participants With Platelet Response up to Week 8 During Part 1
A participant was considered as a responder if he/she met the following response criteria: a Baseline platelet count \<20 Giga cells per liter (Gi/L) and a post-Baseline increased to \>20 Gi/L and at least 2 times the Baseline value; or a Baseline platelet count \>=20 Gi/L and a post-Baseline absolute platelet count increased to \>=50 Gi/L and at least 2 times the Baseline value. The response criteria was evaluated at each visit. Increase in platelet count observed up to 3 days after a platelet transfusion was not considered as a platelet response. The Part 1 Population was comprised of all participants enrolled into Part 1.
Time frame: From Baseline up to Week 8 during Part 1
Population: Part 1 Population: all subjects who enrolled in Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Eltrombopag | Number of Participants With Platelet Response up to Week 8 During Part 1 | 4 Participants |
Secondary
Change in Mean Platelet Count
Time frame: Baseline to Week 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day8 week1 | 3.36 Gi/L | Standard Deviation 11.795 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day15 week2 | 10.41 Gi/L | Standard Deviation 60.225 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day22 week3 | 6.23 Gi/L | Standard Deviation 22.872 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day29 week4 | 5.63 Gi/L | Standard Deviation 17.582 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day36 week5 | 8.58 Gi/L | Standard Deviation 22.504 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day43 week6 | 8.64 Gi/L | Standard Deviation 19.779 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day50 week7 | 9.91 Gi/L | Standard Deviation 25.561 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day57 week8 | 9.67 Gi/L | Standard Deviation 23.243 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day64 week9 | 12.84 Gi/L | Standard Deviation 27.272 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day71 week10 | 15.97 Gi/L | Standard Deviation 33.866 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day78 week11 | 14.42 Gi/L | Standard Deviation 36.901 |
| Part 1: Eltrombopag | Change in Mean Platelet Count | Day 85 week12 | 9.06 Gi/L | Standard Deviation 28.259 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day78 week11 | 6.92 Gi/L | Standard Deviation 26.906 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day8 week1 | 1.66 Gi/L | Standard Deviation 6.249 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day50 week7 | 6.74 Gi/L | Standard Deviation 31.074 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day15 week2 | 3.06 Gi/L | Standard Deviation 9.675 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day71 week10 | 6.23 Gi/L | Standard Deviation 30.941 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day22 week3 | 2.13 Gi/L | Standard Deviation 9.258 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day57 week8 | 7.84 Gi/L | Standard Deviation 34.213 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day29 week4 | 2.44 Gi/L | Standard Deviation 11.215 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day 85 week12 | 4.85 Gi/L | Standard Deviation 26.219 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day36 week5 | 5.9 Gi/L | Standard Deviation 16 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day64 week9 | 6.75 Gi/L | Standard Deviation 31.709 |
| Part 2: Eltrombopag | Change in Mean Platelet Count | Day43 week6 | 5.93 Gi/L | Standard Deviation 21.96 |
Secondary
EQ-5D Utility Score Analysis
EuroQoL Five Dimensions Questionnaire (EQ-5D) is a standardized generic preference based health related quality of life instrument. It records how one's health is today and consists of a descriptive system. The Descriptive system is Comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life. EQ-ED is a score.
Time frame: Change from baseline, up to week 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Eltrombopag | EQ-5D Utility Score Analysis | Week 12 (n=36. n=26) | -0.09 Adjusted mean change from baseline | Standard Error 0.05 |
| Part 1: Eltrombopag | EQ-5D Utility Score Analysis | Week 5 (n=55. n=34) | -0.01 Adjusted mean change from baseline | Standard Error 0.04 |
| Part 1: Eltrombopag | EQ-5D Utility Score Analysis | Week 9 (n=43. n=27) | -0.08 Adjusted mean change from baseline | Standard Error 0.04 |
| Part 2: Eltrombopag | EQ-5D Utility Score Analysis | Week 9 (n=43. n=27) | -0.06 Adjusted mean change from baseline | Standard Error 0.05 |
| Part 2: Eltrombopag | EQ-5D Utility Score Analysis | Week 5 (n=55. n=34) | -0.15 Adjusted mean change from baseline | Standard Error 0.05 |
| Part 2: Eltrombopag | EQ-5D Utility Score Analysis | Week 12 (n=36. n=26) | -0.11 Adjusted mean change from baseline | Standard Error 0.05 |
Secondary
Functional Assessment of Cancer Therapy (FACT)
The FACT-Th-18 is the most widely used and accepted tool evaluating health-related quality-of-life outcomes in cancer patients with chronically low platelets (where Th designates thrombocytopenia). The entire FACT-Th-18 was used in this trial, which includes the 18-item thrombocytopenia subscale used to assess the impact of symptoms, signs, and functional consequences of thrombocytopenia in MDS and AML subjects. The FACT-Th-18 is a validated and reliable instrument with known psychometric properties. FACT-ThS is an 18 item questionnaire specific to assessing the impact of symptoms, signs, and functional consequences of Thrombocytopenia. ThS score ranges from 0 to 72 with higher the score, the better the QoL. FACT G total score moves from 0 to 108 where higher the score, the better the HRQL. FACT-Th Total Score is calculated by adding the FACT-ThS and FACT-G score. Total score ranges from 0 to 180 and again, higher the score, the better the HRQL.
Time frame: Change from baseline, up to week 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTHTOI week 5 (n=61, n=34) | 0.91 Adjusted mean change from baseline | Standard Error 2.04 |
| Part 1: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTG week12 (n=37. n=26) | -3.38 Adjusted mean change from baseline | Standard Error 1.94 |
| Part 1: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTG week 5 (n=61. n=34) | -0.79 Adjusted mean change from baseline | Standard Error 1.64 |
| Part 1: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTHTOI week 9 (n=46, n=28) | -1.69 Adjusted mean change from baseline | Standard Error 2.24 |
| Part 1: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTG week 9 (n=46. n=28) | -4.83 Adjusted mean change from baseline | Standard Error 1.82 |
| Part 1: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTHTOI week 12 (n=37, n=26) | -0.26 Adjusted mean change from baseline | Standard Error 2.37 |
| Part 2: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTG week 9 (n=46. n=28) | -2.76 Adjusted mean change from baseline | Standard Error 2.34 |
| Part 2: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTHTOI week 5 (n=61, n=34) | -2.28 Adjusted mean change from baseline | Standard Error 2.74 |
| Part 2: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTHTOI week 12 (n=37, n=26) | -1.56 Adjusted mean change from baseline | Standard Error 2.95 |
| Part 2: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTG week 5 (n=61. n=34) | -3.15 Adjusted mean change from baseline | Standard Error 2.19 |
| Part 2: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTG week12 (n=37. n=26) | -4.17 Adjusted mean change from baseline | Standard Error 2.39 |
| Part 2: Eltrombopag | Functional Assessment of Cancer Therapy (FACT) | FACTHTOI week 9 (n=46, n=28) | 0.19 Adjusted mean change from baseline | Standard Error 2.89 |
Secondary
Hematologic Improvement
Definitions of hematologic improvement for platelets, neutrophils, and hemoglobin were based on modified International Working Group (IWG) consensus criteria.
Time frame: Weeks 5 to 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Eltrombopag | Hematologic Improvement | Hemoglobin | 0 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Platelets | 8 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Platelets and neutrophils | 2 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Any Improvement | 10 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Platelets and hemoglobin | 0 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Neutrophils | 4 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Platelets, hemoglobin and neutrophils | 0 Number of subjects |
| Part 1: Eltrombopag | Hematologic Improvement | Neutrophils and hemoglobin | 0 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Neutrophils and hemoglobin | 0 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Any Improvement | 4 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Platelets | 2 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Neutrophils | 4 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Hemoglobin | 0 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Platelets and neutrophils | 2 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Platelets and hemoglobin | 0 Number of subjects |
| Part 2: Eltrombopag | Hematologic Improvement | Platelets, hemoglobin and neutrophils | 0 Number of subjects |
Secondary
Independent Reviewer-Assessed Best Response
Participants were evaluated in accordance with the modified International Working Group (Cheson, 2006). CR: Bone marrow blasts \<5%, Hgb ≥11g/dL, Hematologic Improvement - Platelets (Baseline \<20Gi/L: \>20 Gi/L and 2x baseline; Baseline ≥20 Gi/L: ≥50 Gi/L and 2x baseline), Neutrophils ≥1.0 Gi/L, Peripheral blasts 0%. PR: Bone marrow blasts decreased by ≥50% but \>5%, Peripheral blood as in CR. Marrow CR: Bone marrow blasts \<5% and decrease by ≥50%, Note any Hematologic Improvements, Stable disease: Failure to achieve PR, but no evidence of progression for \>8w, Cytogenetic response: Complete: disappearance of chromosomal abnormality; no new abnormalities Partial: ≥50% reduction of chromosomal abnormality.
Time frame: up to week 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Responder | 1 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Morphologic leukemia-free state | 0 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Marrow CR | 1 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Cytogenetic CR | 0 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Molecular CR | 0 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Non-responder | 97 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Stable disease (non-responder) | 18 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Not evaluable (non-responder) | 36 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Complete response (CR) | 0 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Morphologic CR | 0 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Partial response | 0 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Progressive disease (non-responder) | 41 Number of subjects |
| Part 1: Eltrombopag | Independent Reviewer-Assessed Best Response | Missing (non-responder) | 2 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Stable disease (non-responder) | 10 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Complete response (CR) | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Morphologic leukemia-free state | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Missing (non-responder) | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Morphologic CR | 1 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Cytogenetic CR | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Marrow CR | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Molecular CR | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Partial response | 0 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Non-responder | 46 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Progressive disease (non-responder) | 28 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Not evaluable (non-responder) | 8 Number of subjects |
| Part 2: Eltrombopag | Independent Reviewer-Assessed Best Response | Responder | 1 Number of subjects |
Secondary
Independent Reviewer Assessed Disease Progression
Time frame: Up to week 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Part 1: Eltrombopag | Independent Reviewer Assessed Disease Progression | Disease progression | 61 Number of subjects | 21.47 |
| Part 1: Eltrombopag | Independent Reviewer Assessed Disease Progression | No disease progression | 12 Number of subjects | — |
| Part 1: Eltrombopag | Independent Reviewer Assessed Disease Progression | Not evaluable | 23 Number of subjects | — |
| Part 1: Eltrombopag | Independent Reviewer Assessed Disease Progression | Missing | 2 Number of subjects | — |
| Part 2: Eltrombopag | Independent Reviewer Assessed Disease Progression | Missing | 0 Number of subjects | — |
| Part 2: Eltrombopag | Independent Reviewer Assessed Disease Progression | Disease progression | 36 Number of subjects | 19.7 |
| Part 2: Eltrombopag | Independent Reviewer Assessed Disease Progression | Not evaluable | 5 Number of subjects | — |
| Part 2: Eltrombopag | Independent Reviewer Assessed Disease Progression | No disease progression | 6 Number of subjects | — |
Secondary
Maximum Duration of Platelet Transfusion Independence
Time frame: Weeks 5 to 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Eltrombopag | Maximum Duration of Platelet Transfusion Independence | 26.3 maximum duration of platelet transfusion | Standard Deviation 21.47 |
| Part 2: Eltrombopag | Maximum Duration of Platelet Transfusion Independence | 25.4 maximum duration of platelet transfusion | Standard Deviation 19.7 |
Secondary
Mean Number of Platelet Transfusions
Time frame: Weeks 5 to 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Eltrombopag | Mean Number of Platelet Transfusions | 18.8 Number of platelet transfusions | Standard Deviation 18.6 |
| Part 2: Eltrombopag | Mean Number of Platelet Transfusions | 15.7 Number of platelet transfusions | Standard Deviation 20.36 |
Secondary
Median Overall Survival
Time frame: Up to 13 months
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Eltrombopag | Median Overall Survival | 4.27 Months |
| Part 2: Eltrombopag | Median Overall Survival | 4.6 Months |
Secondary
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Occurrence and severity of bleeding, measured using the WHO Bleeding Scale Grade 0=no bleeding; Grade 1=petechiae; Grade 2=mild blood loss; Grade 3=gross blood loss; Grade 4=debilitating blood loss.
Time frame: Weeks 5 to 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 3 (gross blood loss) | 5 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 4 (debilitating blood loss) | 1 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grades 0 - 1 | 46 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 0 (no bleeding) | 15 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grades 1 - 4 | 78 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 2 (mild blood loss) | 41 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grades 2 - 4 | 47 Number of subjects |
| Part 1: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 1 (petechiae) | 31 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grades 2 - 4 | 20 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 1 (petechiae) | 22 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 2 (mild blood loss) | 14 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 0 (no bleeding) | 4 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 3 (gross blood loss) | 3 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grade 4 (debilitating blood loss) | 3 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grades 0 - 1 | 26 Number of subjects |
| Part 2: Eltrombopag | Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale | Grades 1 - 4 | 42 Number of subjects |
Secondary
Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects)
Time frame: Day 1 to week 8
Population: Pharmacokinetic population: all subjects in All Subjects Population who had a PK blood sample obtained/analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Baseline/day 1 (Pre-dose PK) | 0 ug/mL | Standard Deviation 0 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day8 week 1 (Pre-dose PK) | 7.7 ug/mL | Standard Deviation 3.96 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day15 week 2 (Pre-dose PK) | 7.2 ug/mL | Standard Deviation 5.17 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day22 week 3 (Pre-dose PK) | 14.3 ug/mL | Standard Deviation 10.63 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day29 week 3 (2-6hrs post-dose PK) | 20.8 ug/mL | Standard Deviation 14.98 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day36 week 5 (Pre-dose PK) | 20.2 ug/mL | Standard Deviation 16.37 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day43 week6 (2-6hrs post-dose PK) | 41.2 ug/mL | Standard Deviation 32.56 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day50 week 7 (Pre-dose PK) | 30.4 ug/mL | Standard Deviation 27.95 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects) | Day57 week 8 (2-6hrs post-dose PK) | 30.1 ug/mL | Standard Deviation 18.99 |
Secondary
Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects)
Time frame: Day 1 to week 12
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day29 week 4 (Pre-dose PK) | 20.2 ug/mL | Standard Deviation 13.61 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day43 week 6 (Pre-dose PK) | 29.0 ug/mL | Standard Deviation 18.13 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day50 week 7 (2-6hrs post-dose PK) | 42.9 ug/mL | Standard Deviation 22.37 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day57 week8 (Pre-dose PK) | 36.3 ug/mL | Standard Deviation 20.91 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Baseline/day 1 (Pre-dose PK) | 0 ug/mL | Standard Deviation 0 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day15 week 2 (Pre-dose PK) | 10.1 ug/mL | Standard Deviation 5.54 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day22 week 3 (2-6hrs post-dose PK) | 24.0 ug/mL | Standard Deviation 14.6 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day71 week 10 (Pre-dose PK) | 33.5 ug/mL | Standard Deviation 20.4 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day78 week 11 (2-6hrs post-dose PK) | 41.2 ug/mL | Standard Deviation 24.91 |
| Part 1: Eltrombopag | Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects) | Day85 week12 (Pre-dose PK) | 30.7 ug/mL | Standard Deviation 18.03 |
Secondary
Summary of Health Outcomes
The number of subject with medical resource utilization (MRU) data are reported in this table. MRU included number of emergency room visits, number of home healthcare visits, number of hospitalization days, number of medication or surgery specialist visits, number of procedures inpatient, number of procedures outpatient, number of non-study radiology visits, number of non-study laboratory visits, number of nurse practitioner/physician assistance/nurse visits, number of primary care physician visits, number of telephone consultations.
Time frame: week 12
Population: Part 2 Population (Intent-to-Treat population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of telephone consultations (n=17, n=10) | 1 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of hospitalization days (n=17, n=10) | 5 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of emergency room visits (n=17, n=10) | 1 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of med/surg specialist visits (n=17, n=10) | 1 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of non-study radiology visits (n=2, n=2) | 2 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of procedures inpatient (n=17, n=10) | 2 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of non-study laboratory visits (n=17, n=10) | 8 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of procedures outpatient (n=17, n=10) | 1 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of nurse prac/pa/nurse visits (n=17, n=10) | 5 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of home healthcare visits (n=17, n=10) | 2 Subject with Events |
| Part 1: Eltrombopag | Summary of Health Outcomes | Number of primary care physician visits (n=17,10) | 7 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of home healthcare visits (n=17, n=10) | 1 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of non-study radiology visits (n=2, n=2) | 2 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of telephone consultations (n=17, n=10) | 0 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of non-study laboratory visits (n=17, n=10) | 6 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of emergency room visits (n=17, n=10) | 0 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of primary care physician visits (n=17,10) | 1 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of procedures outpatient (n=17, n=10) | 1 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of hospitalization days (n=17, n=10) | 4 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of med/surg specialist visits (n=17, n=10) | 3 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of procedures inpatient (n=17, n=10) | 1 Subject with Events |
| Part 2: Eltrombopag | Summary of Health Outcomes | Number of nurse prac/pa/nurse visits (n=17, n=10) | 3 Subject with Events |