Trial Outcomes & Findings for A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia (NCT NCT01440374)
NCT ID: NCT01440374
Last Updated: 2017-06-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
162 participants
Primary outcome timeframe
From Baseline up to Week 8 during Part 1
Results posted on
2017-06-05
Participant Flow
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.
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.
Participant milestones
| Measure |
Part 1: Eltrombopag
The eltrombopag starting dose the participants received was 100 milligrams (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.
|
Part 2: Placebo
Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study.
|
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.
|
Part 3: Eltrombopag
23 subjects of the 47 randomized to the placebo group in Part 2 entered part 3. 36 subjects of the 98 randomized to the Etrombopag group in Part 2 entered part 3.
All subjects received eltrombopag. Part 3 subjects could also have received treatment for their disease per local SOC, including azacitidine, decitabine, lenalidomide, and chemotherapy. The duration of Part 3 was to be 10 months for subjects from Part 1and 9 months for subjects from Part 2.
|
|---|---|---|---|---|
|
Part 1: Open-label Phase
STARTED
|
17
|
0
|
0
|
0
|
|
Part 1: Open-label Phase
COMPLETED
|
11
|
0
|
0
|
0
|
|
Part 1: Open-label Phase
NOT COMPLETED
|
6
|
0
|
0
|
0
|
|
Part 2; Double-blind Phase
STARTED
|
0
|
47
|
98
|
0
|
|
Part 2; Double-blind Phase
COMPLETED
|
0
|
27
|
43
|
0
|
|
Part 2; Double-blind Phase
NOT COMPLETED
|
0
|
20
|
55
|
0
|
|
Part 3: Extension
STARTED
|
0
|
0
|
0
|
59
|
|
Part 3: Extension
COMPLETED
|
0
|
0
|
0
|
27
|
|
Part 3: Extension
NOT COMPLETED
|
0
|
0
|
0
|
32
|
Reasons for withdrawal
| Measure |
Part 1: Eltrombopag
The eltrombopag starting dose the participants received was 100 milligrams (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.
|
Part 2: Placebo
Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study.
|
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.
|
Part 3: Eltrombopag
23 subjects of the 47 randomized to the placebo group in Part 2 entered part 3. 36 subjects of the 98 randomized to the Etrombopag group in Part 2 entered part 3.
All subjects received eltrombopag. Part 3 subjects could also have received treatment for their disease per local SOC, including azacitidine, decitabine, lenalidomide, and chemotherapy. The duration of Part 3 was to be 10 months for subjects from Part 1and 9 months for subjects from Part 2.
|
|---|---|---|---|---|
|
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
Physician Decision
|
0
|
8
|
17
|
0
|
|
Part 2; Double-blind Phase
Withdrawal by Subject
|
0
|
4
|
5
|
0
|
|
Part 2; Double-blind Phase
Protocol Violation
|
0
|
0
|
1
|
0
|
|
Part 2; Double-blind Phase
Lack of Efficacy
|
0
|
1
|
0
|
0
|
|
Part 2; Double-blind Phase
Adverse Event
|
0
|
7
|
31
|
0
|
|
Part 2; Double-blind Phase
Not treated
|
0
|
0
|
1
|
0
|
|
Part 3: Extension
Withdrawal by Subject
|
0
|
0
|
0
|
5
|
|
Part 3: Extension
Adverse Event
|
0
|
0
|
0
|
13
|
|
Part 3: Extension
Physician Decision
|
0
|
0
|
0
|
14
|
Baseline Characteristics
A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Part 1: Eltrombopag
n=17 Participants
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.
|
Part 2: Placebo
n=47 Participants
Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study.
|
Part 2: Eltrombopag
n=98 Participants
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.
|
Total
n=162 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
71.5 Years
STANDARD_DEVIATION 10.78 • n=93 Participants
|
70.6 Years
STANDARD_DEVIATION 10.72 • n=4 Participants
|
72.3 Years
STANDARD_DEVIATION 8.94 • n=27 Participants
|
71.8 Years
STANDARD_DEVIATION 9.56 • n=483 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
55 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
107 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
3 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
17 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
14 Participants
n=93 Participants
|
39 Participants
n=4 Participants
|
81 Participants
n=27 Participants
|
134 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: From Baseline up to Week 8 during Part 1Population: Part 1 Population: all subjects who enrolled in 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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=17 Participants
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.
|
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.
|
|---|---|---|
|
Number of Participants With Platelet Response up to Week 8 During Part 1
|
4 Participants
|
—
|
PRIMARY outcome
Timeframe: From Week 5 up to Week 12 during Part 2Population: Part 2 Population (Intent-To-Treat (ITT) Population: all randomized subjects in 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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=47 Participants
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.
|
Part 2: Eltrombopag
n=98 Participants
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.
|
|---|---|---|
|
Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2
|
69 percentages of participants
Interval 57.0 to 80.0
|
54 percentages of participants
Interval 43.0 to 64.0
|
SECONDARY outcome
Timeframe: Day 1 to week 8Population: Pharmacokinetic population: all subjects in All Subjects Population who had a PK blood sample obtained/analyzed.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=17 Participants
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.
|
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.
|
|---|---|---|
|
Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects)
Baseline/day 1 (Pre-dose PK)
|
0 ug/mL
Standard Deviation 0
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Day 1 to week 12Population: Pharmacokinetic population
Outcome measures
| Measure |
Part 1: Eltrombopag
n=97 Participants
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.
|
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.
|
|---|---|---|
|
Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects)
Baseline/day 1 (Pre-dose PK)
|
0 ug/mL
Standard Deviation 0
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects)
Day57 week8 (Pre-dose PK)
|
36.3 ug/mL
Standard Deviation 20.91
|
—
|
|
Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects)
Day71 week 10 (Pre-dose PK)
|
33.5 ug/mL
Standard Deviation 20.40
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Weeks 5 to 12Population: Part 2 Population (Intent-to-Treat population)
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Mean Number of Platelet Transfusions
|
18.8 Number of platelet transfusions
Standard Deviation 18.60
|
15.7 Number of platelet transfusions
Standard Deviation 20.36
|
SECONDARY outcome
Timeframe: Weeks 5 to 12Population: Part 2 Population (Intent-to-Treat population)
Definitions of hematologic improvement for platelets, neutrophils, and hemoglobin were based on modified International Working Group (IWG) consensus criteria.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Hematologic Improvement
Any Improvement
|
10 Number of subjects
|
4 Number of subjects
|
|
Hematologic Improvement
Platelets and hemoglobin
|
0 Number of subjects
|
0 Number of subjects
|
|
Hematologic Improvement
Platelets, hemoglobin and neutrophils
|
0 Number of subjects
|
0 Number of subjects
|
|
Hematologic Improvement
Platelets
|
8 Number of subjects
|
2 Number of subjects
|
|
Hematologic Improvement
Neutrophils
|
4 Number of subjects
|
4 Number of subjects
|
|
Hematologic Improvement
Hemoglobin
|
0 Number of subjects
|
0 Number of subjects
|
|
Hematologic Improvement
Platelets and neutrophils
|
2 Number of subjects
|
2 Number of subjects
|
|
Hematologic Improvement
Neutrophils and hemoglobin
|
0 Number of subjects
|
0 Number of subjects
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: Part 2 Population (Intent-to-Treat population)
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Change in Mean Platelet Count
Day8 week1
|
3.36 Gi/L
Standard Deviation 11.795
|
1.66 Gi/L
Standard Deviation 6.249
|
|
Change in Mean Platelet Count
Day15 week2
|
10.41 Gi/L
Standard Deviation 60.225
|
3.06 Gi/L
Standard Deviation 9.675
|
|
Change in Mean Platelet Count
Day22 week3
|
6.23 Gi/L
Standard Deviation 22.872
|
2.13 Gi/L
Standard Deviation 9.258
|
|
Change in Mean Platelet Count
Day29 week4
|
5.63 Gi/L
Standard Deviation 17.582
|
2.44 Gi/L
Standard Deviation 11.215
|
|
Change in Mean Platelet Count
Day36 week5
|
8.58 Gi/L
Standard Deviation 22.504
|
5.9 Gi/L
Standard Deviation 16.000
|
|
Change in Mean Platelet Count
Day43 week6
|
8.64 Gi/L
Standard Deviation 19.779
|
5.93 Gi/L
Standard Deviation 21.960
|
|
Change in Mean Platelet Count
Day50 week7
|
9.91 Gi/L
Standard Deviation 25.561
|
6.74 Gi/L
Standard Deviation 31.074
|
|
Change in Mean Platelet Count
Day57 week8
|
9.67 Gi/L
Standard Deviation 23.243
|
7.84 Gi/L
Standard Deviation 34.213
|
|
Change in Mean Platelet Count
Day64 week9
|
12.84 Gi/L
Standard Deviation 27.272
|
6.75 Gi/L
Standard Deviation 31.709
|
|
Change in Mean Platelet Count
Day71 week10
|
15.97 Gi/L
Standard Deviation 33.866
|
6.23 Gi/L
Standard Deviation 30.941
|
|
Change in Mean Platelet Count
Day78 week11
|
14.42 Gi/L
Standard Deviation 36.901
|
6.92 Gi/L
Standard Deviation 26.906
|
|
Change in Mean Platelet Count
Day 85 week12
|
9.06 Gi/L
Standard Deviation 28.259
|
4.85 Gi/L
Standard Deviation 26.219
|
SECONDARY outcome
Timeframe: Weeks 5 to 12Population: Part 2 Population (Intent-to-Treat population)
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Maximum Duration of Platelet Transfusion Independence
|
26.3 maximum duration of platelet transfusion
Standard Deviation 21.47
|
25.4 maximum duration of platelet transfusion
Standard Deviation 19.70
|
SECONDARY outcome
Timeframe: Weeks 5 to 12Population: Part 2 Population (Intent-to-Treat population)
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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grades 0 - 1
|
46 Number of subjects
|
26 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grades 1 - 4
|
78 Number of subjects
|
42 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grade 0 (no bleeding)
|
15 Number of subjects
|
4 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grade 1 (petechiae)
|
31 Number of subjects
|
22 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grade 2 (mild blood loss)
|
41 Number of subjects
|
14 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grade 3 (gross blood loss)
|
5 Number of subjects
|
3 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grade 4 (debilitating blood loss)
|
1 Number of subjects
|
3 Number of subjects
|
|
Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale
Grades 2 - 4
|
47 Number of subjects
|
20 Number of subjects
|
SECONDARY outcome
Timeframe: up to week 12Population: Part 2 Population (Intent-to-Treat population)
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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Independent Reviewer-Assessed Best Response
Morphologic CR
|
0 Number of subjects
|
1 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Cytogenetic CR
|
0 Number of subjects
|
0 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Molecular CR
|
0 Number of subjects
|
0 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Not evaluable (non-responder)
|
36 Number of subjects
|
8 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Responder
|
1 Number of subjects
|
1 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Complete response (CR)
|
0 Number of subjects
|
0 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Morphologic leukemia-free state
|
0 Number of subjects
|
0 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Marrow CR
|
1 Number of subjects
|
0 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Non-responder
|
97 Number of subjects
|
46 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Partial response
|
0 Number of subjects
|
0 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Stable disease (non-responder)
|
18 Number of subjects
|
10 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Progressive disease (non-responder)
|
41 Number of subjects
|
28 Number of subjects
|
|
Independent Reviewer-Assessed Best Response
Missing (non-responder)
|
2 Number of subjects
|
0 Number of subjects
|
SECONDARY outcome
Timeframe: Up to week 12Population: Part 2 Population (Intent-to-Treat population)
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Independent Reviewer Assessed Disease Progression
Not evaluable
|
23 Number of subjects
|
5 Number of subjects
|
|
Independent Reviewer Assessed Disease Progression
Disease progression
|
61 Number of subjects
21.47
|
36 Number of subjects
19.70
|
|
Independent Reviewer Assessed Disease Progression
No disease progression
|
12 Number of subjects
|
6 Number of subjects
|
|
Independent Reviewer Assessed Disease Progression
Missing
|
2 Number of subjects
|
0 Number of subjects
|
SECONDARY outcome
Timeframe: Up to 13 monthsPopulation: Part 2 Population (Intent-to-Treat population)
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Median Overall Survival
|
4.27 Months
Interval 2.96 to 7.59
|
4.6 Months
Interval 3.29 to 7.82
|
SECONDARY outcome
Timeframe: week 12Population: Part 2 Population (Intent-to-Treat population)
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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Summary of Health Outcomes
Number of med/surg specialist visits (n=17, n=10)
|
1 Subject with Events
|
3 Subject with Events
|
|
Summary of Health Outcomes
Number of emergency room visits (n=17, n=10)
|
1 Subject with Events
|
0 Subject with Events
|
|
Summary of Health Outcomes
Number of home healthcare visits (n=17, n=10)
|
2 Subject with Events
|
1 Subject with Events
|
|
Summary of Health Outcomes
Number of hospitalization days (n=17, n=10)
|
5 Subject with Events
|
4 Subject with Events
|
|
Summary of Health Outcomes
Number of procedures inpatient (n=17, n=10)
|
2 Subject with Events
|
1 Subject with Events
|
|
Summary of Health Outcomes
Number of procedures outpatient (n=17, n=10)
|
1 Subject with Events
|
1 Subject with Events
|
|
Summary of Health Outcomes
Number of non-study radiology visits (n=2, n=2)
|
2 Subject with Events
|
2 Subject with Events
|
|
Summary of Health Outcomes
Number of nurse prac/pa/nurse visits (n=17, n=10)
|
5 Subject with Events
|
3 Subject with Events
|
|
Summary of Health Outcomes
Number of primary care physician visits (n=17,10)
|
7 Subject with Events
|
1 Subject with Events
|
|
Summary of Health Outcomes
Number of telephone consultations (n=17, n=10)
|
1 Subject with Events
|
0 Subject with Events
|
|
Summary of Health Outcomes
Number of non-study laboratory visits (n=17, n=10)
|
8 Subject with Events
|
6 Subject with Events
|
SECONDARY outcome
Timeframe: Change from baseline, up to week 12Population: Part 2 Population (Intent-to-Treat population)
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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
Functional Assessment of Cancer Therapy (FACT)
FACTG week 5 (n=61. n=34)
|
-0.79 Adjusted mean change from baseline
Standard Error 1.64
|
-3.15 Adjusted mean change from baseline
Standard Error 2.19
|
|
Functional Assessment of Cancer Therapy (FACT)
FACTG week 9 (n=46. n=28)
|
-4.83 Adjusted mean change from baseline
Standard Error 1.82
|
-2.76 Adjusted mean change from baseline
Standard Error 2.34
|
|
Functional Assessment of Cancer Therapy (FACT)
FACTG week12 (n=37. n=26)
|
-3.38 Adjusted mean change from baseline
Standard Error 1.94
|
-4.17 Adjusted mean change from baseline
Standard Error 2.39
|
|
Functional Assessment of Cancer Therapy (FACT)
FACTHTOI week 5 (n=61, n=34)
|
0.91 Adjusted mean change from baseline
Standard Error 2.04
|
-2.28 Adjusted mean change from baseline
Standard Error 2.74
|
|
Functional Assessment of Cancer Therapy (FACT)
FACTHTOI week 9 (n=46, n=28)
|
-1.69 Adjusted mean change from baseline
Standard Error 2.24
|
0.19 Adjusted mean change from baseline
Standard Error 2.89
|
|
Functional Assessment of Cancer Therapy (FACT)
FACTHTOI week 12 (n=37, n=26)
|
-0.26 Adjusted mean change from baseline
Standard Error 2.37
|
-1.56 Adjusted mean change from baseline
Standard Error 2.95
|
SECONDARY outcome
Timeframe: Change from baseline, up to week 12Population: Part 2 Population (Intent-to-Treat population)
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.
Outcome measures
| Measure |
Part 1: Eltrombopag
n=98 Participants
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.
|
Part 2: Eltrombopag
n=47 Participants
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.
|
|---|---|---|
|
EQ-5D Utility Score Analysis
Week 5 (n=55. n=34)
|
-0.01 Adjusted mean change from baseline
Standard Error 0.04
|
-0.15 Adjusted mean change from baseline
Standard Error 0.05
|
|
EQ-5D Utility Score Analysis
Week 9 (n=43. n=27)
|
-0.08 Adjusted mean change from baseline
Standard Error 0.04
|
-0.06 Adjusted mean change from baseline
Standard Error 0.05
|
|
EQ-5D Utility Score Analysis
Week 12 (n=36. n=26)
|
-0.09 Adjusted mean change from baseline
Standard Error 0.05
|
-0.11 Adjusted mean change from baseline
Standard Error 0.05
|
Adverse Events
Eltrombopag, Part 1 Subjects
Serious events: 9 serious events
Other events: 17 other events
Deaths: 0 deaths
Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects
Serious events: 56 serious events
Other events: 89 other events
Deaths: 0 deaths
Placebo, Part 2 Plus 1 Day From Part 2 Subjects
Serious events: 32 serious events
Other events: 44 other events
Deaths: 0 deaths
Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects
Serious events: 39 serious events
Other events: 54 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eltrombopag, Part 1 Subjects
n=17 participants at risk
Eltrombopag, Part 1 subjects
|
Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects
n=97 participants at risk
Eltrombopag, Part 2 plus 1 day from Part 2 subjects
|
Placebo, Part 2 Plus 1 Day From Part 2 Subjects
n=47 participants at risk
Placebo, Part 2 plus 1 day from Part 2 subjects
|
Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects
n=59 participants at risk
Eltrombopag, Part 3 plus 30 Days from Part 2 subjects
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/17
|
2.1%
2/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/17
|
7.2%
7/97
|
14.9%
7/47
|
10.2%
6/59
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
5.1%
3/59
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Blood and lymphatic system disorders
Splenic artery thrombosis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/17
|
1.0%
1/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Cardiac disorders
Palpitations
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Endocrine disorders
Adrenal disorder
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Eye disorders
Retinal vein occlusion
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Eye disorders
Vitreous haemorrhage
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Abdominal pain
|
5.9%
1/17
|
2.1%
2/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/17
|
2.1%
2/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/17
|
1.0%
1/97
|
6.4%
3/47
|
1.7%
1/59
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/17
|
2.1%
2/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Gastrointestinal hypomotility
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Oral mucosal blistering
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
3.4%
2/59
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
1.7%
1/59
|
|
General disorders
Asthenia
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
3.4%
2/59
|
|
General disorders
Chest discomfort
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
General disorders
Chills
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
General disorders
Death
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
General disorders
Disease progression
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
General disorders
Fatigue
|
0.00%
0/17
|
1.0%
1/97
|
2.1%
1/47
|
1.7%
1/59
|
|
General disorders
General physical health deterioration
|
0.00%
0/17
|
2.1%
2/97
|
4.3%
2/47
|
3.4%
2/59
|
|
General disorders
Malaise
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
General disorders
Multi-organ failure
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/17
|
0.00%
0/97
|
4.3%
2/47
|
0.00%
0/59
|
|
General disorders
Pyrexia
|
11.8%
2/17
|
7.2%
7/97
|
12.8%
6/47
|
11.9%
7/59
|
|
General disorders
Sudden death
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Abscess neck
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Appendicitis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Bronchitis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
6.8%
4/59
|
|
Infections and infestations
Catheter site cellulitis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Cellulitis
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Cholecystitis infective
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Cystitis
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Device related infection
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Endocarditis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Enteritis infectious
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Infection
|
0.00%
0/17
|
2.1%
2/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Influenza
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/17
|
2.1%
2/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Lung infection
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Otitis externa
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Pneumonia
|
5.9%
1/17
|
14.4%
14/97
|
10.6%
5/47
|
16.9%
10/59
|
|
Infections and infestations
Respiratory tract infection
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Sepsis
|
23.5%
4/17
|
8.2%
8/97
|
10.6%
5/47
|
10.2%
6/59
|
|
Infections and infestations
Septic shock
|
11.8%
2/17
|
1.0%
1/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Infections and infestations
Splenic abscess
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Infections and infestations
Streptococcal sepsis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Tooth infection
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/17
|
3.1%
3/97
|
2.1%
1/47
|
8.5%
5/59
|
|
Infections and infestations
Urosepsis
|
0.00%
0/17
|
1.0%
1/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Viral oesophagitis
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Alanine aminotransferase increased
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Investigations
International normalised ratio increased
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Investigations
White blood cell count increased
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
3.4%
2/59
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.00%
0/17
|
2.1%
2/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Cerebral haemorrhage
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/17
|
1.0%
1/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Nervous system disorders
Seizure
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Nervous system disorders
Syncope
|
0.00%
0/17
|
2.1%
2/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Renal and urinary disorders
Haematuria
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.9%
1/17
|
2.1%
2/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Vascular disorders
Haematoma
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Vascular disorders
Hypotension
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
Other adverse events
| Measure |
Eltrombopag, Part 1 Subjects
n=17 participants at risk
Eltrombopag, Part 1 subjects
|
Eltrombopag, Part 2 Plus 1 Day From Part 2 Subjects
n=97 participants at risk
Eltrombopag, Part 2 plus 1 day from Part 2 subjects
|
Placebo, Part 2 Plus 1 Day From Part 2 Subjects
n=47 participants at risk
Placebo, Part 2 plus 1 day from Part 2 subjects
|
Eltrombopag, Part 3 Plus 30 Days From Part 2 Subjects
n=59 participants at risk
Eltrombopag, Part 3 plus 30 Days from Part 2 subjects
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
17.6%
3/17
|
8.2%
8/97
|
4.3%
2/47
|
3.4%
2/59
|
|
Blood and lymphatic system disorders
Blood disorder
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.9%
1/17
|
4.1%
4/97
|
0.00%
0/47
|
3.4%
2/59
|
|
Blood and lymphatic system disorders
Haemolysis
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/17
|
3.1%
3/97
|
2.1%
1/47
|
6.8%
4/59
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.9%
1/17
|
2.1%
2/97
|
4.3%
2/47
|
5.1%
3/59
|
|
Cardiac disorders
Pericardial effusion
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Ear and labyrinth disorders
Hypoacusis
|
5.9%
1/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Ear and labyrinth disorders
Vertigo
|
5.9%
1/17
|
1.0%
1/97
|
4.3%
2/47
|
3.4%
2/59
|
|
Eye disorders
Conjunctival haemorrhage
|
5.9%
1/17
|
2.1%
2/97
|
8.5%
4/47
|
0.00%
0/59
|
|
Eye disorders
Eye haemorrhage
|
0.00%
0/17
|
5.2%
5/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Eye disorders
Ocular hyperaemia
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Eye disorders
Ocular icterus
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
8.5%
5/59
|
|
Gastrointestinal disorders
Abdominal pain
|
5.9%
1/17
|
6.2%
6/97
|
6.4%
3/47
|
8.5%
5/59
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/17
|
6.2%
6/97
|
4.3%
2/47
|
3.4%
2/59
|
|
Gastrointestinal disorders
Colitis
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Constipation
|
17.6%
3/17
|
12.4%
12/97
|
0.00%
0/47
|
11.9%
7/59
|
|
Gastrointestinal disorders
Diarrhoea
|
23.5%
4/17
|
20.6%
20/97
|
10.6%
5/47
|
18.6%
11/59
|
|
Gastrointestinal disorders
Gingival bleeding
|
5.9%
1/17
|
13.4%
13/97
|
17.0%
8/47
|
11.9%
7/59
|
|
Gastrointestinal disorders
Gingival swelling
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.00%
0/17
|
9.3%
9/97
|
14.9%
7/47
|
11.9%
7/59
|
|
Gastrointestinal disorders
Nausea
|
5.9%
1/17
|
13.4%
13/97
|
17.0%
8/47
|
23.7%
14/59
|
|
Gastrointestinal disorders
Vomiting
|
11.8%
2/17
|
6.2%
6/97
|
10.6%
5/47
|
10.2%
6/59
|
|
General disorders
Asthenia
|
17.6%
3/17
|
4.1%
4/97
|
10.6%
5/47
|
10.2%
6/59
|
|
General disorders
Catheter site related reaction
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
General disorders
Fatigue
|
5.9%
1/17
|
23.7%
23/97
|
6.4%
3/47
|
15.3%
9/59
|
|
General disorders
Oedema peripheral
|
0.00%
0/17
|
9.3%
9/97
|
6.4%
3/47
|
11.9%
7/59
|
|
General disorders
Pain
|
5.9%
1/17
|
2.1%
2/97
|
2.1%
1/47
|
3.4%
2/59
|
|
General disorders
Pyrexia
|
23.5%
4/17
|
18.6%
18/97
|
21.3%
10/47
|
20.3%
12/59
|
|
General disorders
Xerosis
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Hepatobiliary disorders
Hepatotoxicity
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
5.9%
1/17
|
3.1%
3/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Immune system disorders
Drug hypersensitivity
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Acute sinusitis
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Arthritis infective
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Bacterial infection
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Cellulitis
|
0.00%
0/17
|
2.1%
2/97
|
6.4%
3/47
|
3.4%
2/59
|
|
Infections and infestations
Escherichia infection
|
5.9%
1/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Infections and infestations
Klebsiella sepsis
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
11.9%
7/59
|
|
Infections and infestations
Otitis externa
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Infections and infestations
Pneumonia
|
23.5%
4/17
|
3.1%
3/97
|
2.1%
1/47
|
3.4%
2/59
|
|
Infections and infestations
Skin infection
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Infections and infestations
Upper respiratory tract infection
|
17.6%
3/17
|
2.1%
2/97
|
4.3%
2/47
|
0.00%
0/59
|
|
Infections and infestations
Urinary tract infection
|
5.9%
1/17
|
5.2%
5/97
|
4.3%
2/47
|
5.1%
3/59
|
|
Injury, poisoning and procedural complications
Contusion
|
5.9%
1/17
|
4.1%
4/97
|
6.4%
3/47
|
8.5%
5/59
|
|
Injury, poisoning and procedural complications
Fall
|
5.9%
1/17
|
1.0%
1/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Injury, poisoning and procedural complications
Laceration
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/17
|
2.1%
2/97
|
6.4%
3/47
|
1.7%
1/59
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/17
|
0.00%
0/97
|
0.00%
0/47
|
5.1%
3/59
|
|
Investigations
Activated partial thromboplastin time prolonged
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Alanine aminotransferase increased
|
17.6%
3/17
|
10.3%
10/97
|
10.6%
5/47
|
8.5%
5/59
|
|
Investigations
Aspartate aminotransferase increased
|
5.9%
1/17
|
3.1%
3/97
|
10.6%
5/47
|
3.4%
2/59
|
|
Investigations
Blood albumin decreased
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Investigations
Blood alkaline phosphatase increased
|
5.9%
1/17
|
2.1%
2/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Investigations
Blood bilirubin increased
|
5.9%
1/17
|
6.2%
6/97
|
4.3%
2/47
|
8.5%
5/59
|
|
Investigations
Blood phosphorus decreased
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Investigations
Blood sodium increased
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Blood urea increased
|
0.00%
0/17
|
2.1%
2/97
|
6.4%
3/47
|
3.4%
2/59
|
|
Investigations
Body temperature fluctuation
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Investigations
Liver function test abnormal
|
5.9%
1/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Investigations
Platelet count decreased
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Serum ferritin increased
|
11.8%
2/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Investigations
Weight decreased
|
5.9%
1/17
|
1.0%
1/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.8%
2/17
|
14.4%
14/97
|
14.9%
7/47
|
16.9%
10/59
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/17
|
2.1%
2/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.9%
1/17
|
7.2%
7/97
|
4.3%
2/47
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
5.9%
1/17
|
4.1%
4/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/17
|
9.3%
9/97
|
6.4%
3/47
|
13.6%
8/59
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.9%
1/17
|
5.2%
5/97
|
0.00%
0/47
|
5.1%
3/59
|
|
Metabolism and nutrition disorders
Hypophagia
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.9%
1/17
|
2.1%
2/97
|
0.00%
0/47
|
3.4%
2/59
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.9%
1/17
|
1.0%
1/97
|
8.5%
4/47
|
3.4%
2/59
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/17
|
11.3%
11/97
|
8.5%
4/47
|
8.5%
5/59
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/17
|
6.2%
6/97
|
10.6%
5/47
|
3.4%
2/59
|
|
Nervous system disorders
Aphonia
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Balance disorder
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Dizziness
|
11.8%
2/17
|
9.3%
9/97
|
8.5%
4/47
|
3.4%
2/59
|
|
Nervous system disorders
Headache
|
17.6%
3/17
|
3.1%
3/97
|
6.4%
3/47
|
1.7%
1/59
|
|
Nervous system disorders
Mental impairment
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Nervous system disorders
Poor quality sleep
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Nervous system disorders
Syncope
|
11.8%
2/17
|
0.00%
0/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Psychiatric disorders
Anxiety
|
5.9%
1/17
|
2.1%
2/97
|
0.00%
0/47
|
3.4%
2/59
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/17
|
1.0%
1/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Psychiatric disorders
Initial insomnia
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Renal and urinary disorders
Azotaemia
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Renal and urinary disorders
Urinary incontinence
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Renal and urinary disorders
Urinary retention
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
5.9%
1/17
|
2.1%
2/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17
|
13.4%
13/97
|
8.5%
4/47
|
11.9%
7/59
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.9%
1/17
|
9.3%
9/97
|
10.6%
5/47
|
6.8%
4/59
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
29.4%
5/17
|
27.8%
27/97
|
23.4%
11/47
|
20.3%
12/59
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/17
|
6.2%
6/97
|
6.4%
3/47
|
3.4%
2/59
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.9%
1/17
|
0.00%
0/97
|
4.3%
2/47
|
5.1%
3/59
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
5.9%
1/17
|
0.00%
0/97
|
2.1%
1/47
|
0.00%
0/59
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
5.9%
1/17
|
0.00%
0/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Blood blister
|
0.00%
0/17
|
0.00%
0/97
|
2.1%
1/47
|
5.1%
3/59
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
1.7%
1/59
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/17
|
1.0%
1/97
|
0.00%
0/47
|
5.1%
3/59
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
11.8%
2/17
|
7.2%
7/97
|
12.8%
6/47
|
10.2%
6/59
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
35.3%
6/17
|
42.3%
41/97
|
23.4%
11/47
|
13.6%
8/59
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
1/17
|
2.1%
2/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Skin and subcutaneous tissue disorders
Purpura
|
5.9%
1/17
|
0.00%
0/97
|
4.3%
2/47
|
3.4%
2/59
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.9%
1/17
|
0.00%
0/97
|
2.1%
1/47
|
1.7%
1/59
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
11.8%
2/17
|
2.1%
2/97
|
0.00%
0/47
|
5.1%
3/59
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.00%
0/17
|
2.1%
2/97
|
6.4%
3/47
|
0.00%
0/59
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
5.9%
1/17
|
1.0%
1/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Vascular disorders
Haematoma
|
0.00%
0/17
|
7.2%
7/97
|
19.1%
9/47
|
15.3%
9/59
|
|
Vascular disorders
Haemorrhage
|
11.8%
2/17
|
4.1%
4/97
|
8.5%
4/47
|
1.7%
1/59
|
|
Vascular disorders
Hypertension
|
0.00%
0/17
|
6.2%
6/97
|
0.00%
0/47
|
0.00%
0/59
|
|
Vascular disorders
Hypotension
|
5.9%
1/17
|
3.1%
3/97
|
2.1%
1/47
|
3.4%
2/59
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER