Trial Outcomes & Findings for A Study to Assess the Safety and Efficacy of Eltrombopag in Japanese Subjects With Refractory, Moderate or More Severe Aplastic Anemia (NCT NCT02148133)
NCT ID: NCT02148133
Last Updated: 2019-05-03
Results Overview
Hematologic response rate at 6 months (at WeeK 26) after the start of study treatment was defined as the percentage of subjects who met any of the response criteria (Platelet count, Hemoglobin level, Neutrophil count). 1 ) Platelet count: an increase from baseline by 20,000/μL or more (In the absence of platelet transfusion), or no platelet transfusion requirements for 8 weeks; 2) Hemoglobin: When the baseline hemoglobin level is \<9 g/dL: Without RBC transfusion at baseline, an increase from baseline by 1.5 g/dL or more; With RBC transfusion at baseline, a decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period (1 unit = RBC derived from 200 mL blood); 3) Neutrophil count: an increase from baseline by 500/μL or more (in the absence of granulocyte colony-stimulating factor (G-CSF)), or (if \< 500/μL at baseline) an increase by 100 % or more. Only descriptive analysis done.
COMPLETED
PHASE2
21 participants
D183 (Week 26)
2019-05-03
Participant Flow
The study took place in 12 clinical sites in Japan
The target number of subjects enrolled was 20. A total 36 subjects were screened and 21 were enrolled in the study. All 21 subjects enrolled received at least 1 dose of study treatment and were included in the planned analysis sets (full analysis set, safety population and pharmacokinetic population).
Participant milestones
| Measure |
Eltrombopag
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
Safety Set (SS)
|
21
|
|
Overall Study
Pharmacokinetic Analysis Set (PAS)
|
21
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Eltrombopag
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
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|---|---|
|
Overall Study
Investigator discretion
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Protocol deviation
|
1
|
|
Overall Study
Protocol-defined stopping criteria
|
2
|
Baseline Characteristics
A Study to Assess the Safety and Efficacy of Eltrombopag in Japanese Subjects With Refractory, Moderate or More Severe Aplastic Anemia
Baseline characteristics by cohort
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
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|---|---|
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Age, Continuous
|
53.0 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: D183 (Week 26)Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
Hematologic response rate at 6 months (at WeeK 26) after the start of study treatment was defined as the percentage of subjects who met any of the response criteria (Platelet count, Hemoglobin level, Neutrophil count). 1 ) Platelet count: an increase from baseline by 20,000/μL or more (In the absence of platelet transfusion), or no platelet transfusion requirements for 8 weeks; 2) Hemoglobin: When the baseline hemoglobin level is \<9 g/dL: Without RBC transfusion at baseline, an increase from baseline by 1.5 g/dL or more; With RBC transfusion at baseline, a decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period (1 unit = RBC derived from 200 mL blood); 3) Neutrophil count: an increase from baseline by 500/μL or more (in the absence of granulocyte colony-stimulating factor (G-CSF)), or (if \< 500/μL at baseline) an increase by 100 % or more. Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Hematological Response at Week 26
|
47.6 Percentage of participants
Interval 25.7 to 70.2
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The changes in observed values for Platelet Count were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
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|---|---|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Baseline
|
12.19 Giga/Liter (Gi/L)
Standard Deviation 7.155
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
D92 Week13
|
6.32 Giga/Liter (Gi/L)
Standard Deviation 7.698
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
D183 Week26
|
13.09 Giga/Liter (Gi/L)
Standard Deviation 14.015
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Extension W39
|
23.50 Giga/Liter (Gi/L)
Standard Deviation 22.037
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Extension W52
|
21.50 Giga/Liter (Gi/L)
Standard Deviation 15.720
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Extension W78
|
36.69 Giga/Liter (Gi/L)
Standard Deviation 23.798
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Extension W104
|
35.79 Giga/Liter (Gi/L)
Standard Deviation 21.389
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Extension W130
|
42.79 Giga/Liter (Gi/L)
Standard Deviation 28.795
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Extension W156
|
25.50 Giga/Liter (Gi/L)
Standard Deviation NA
Not calculated
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Withdrawal
|
8.81 Giga/Liter (Gi/L)
Standard Deviation 19.387
|
|
Change in Platelet Count From Baseline in the Absence of Platelet Transfusion Over Time
Last Assessment On-Therapy
|
18.38 Giga/Liter (Gi/L)
Standard Deviation 24.017
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The changes in observed values for Hemoglobin were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Baseline
|
70.4 Gram/Liter (g/L)
Standard Deviation 13.95
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
D92 Week13
|
4.9 Gram/Liter (g/L)
Standard Deviation 11.91
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
D183 Week26
|
8.8 Gram/Liter (g/L)
Standard Deviation 17.08
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Extension W39
|
19.3 Gram/Liter (g/L)
Standard Deviation 22.29
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Extension W52
|
24.0 Gram/Liter (g/L)
Standard Deviation 21.11
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Extension W78
|
32.8 Gram/Liter (g/L)
Standard Deviation 19.58
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Extension W104
|
34.4 Gram/Liter (g/L)
Standard Deviation 20.44
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Extension W130
|
31.6 Gram/Liter (g/L)
Standard Deviation 16.99
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Extension W156
|
16.0 Gram/Liter (g/L)
Standard Deviation NA
Not calculated
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Withdrawal
|
-3.0 Gram/Liter (g/L)
Standard Deviation 13.85
|
|
Change in Hemoglobin From Baseline in the Absence of Red Blood Cell (RBC) Transfusion Over Time
Last Assessment On-Therapy
|
10.0 Gram/Liter (g/L)
Standard Deviation 20.14
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The changes in observed values for Neutrophil Count were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Baseline
|
0.8247 Giga/Liter (Gi/L)
Standard Deviation 0.47985
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
D92 Week13
|
0.3321 Giga/Liter (Gi/L)
Standard Deviation 0.51398
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
D183 Week26
|
0.2046 Giga/Liter (Gi/L)
Standard Deviation 0.43640
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Extension W39
|
0.4537 Giga/Liter (Gi/L)
Standard Deviation 0.87231
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Extension W52
|
0.5236 Giga/Liter (Gi/L)
Standard Deviation 0.58529
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Extension W78
|
0.8579 Giga/Liter (Gi/L)
Standard Deviation 0.62320
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Extension W104
|
0.6312 Giga/Liter (Gi/L)
Standard Deviation 1.05205
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Extension W130
|
1.1835 Giga/Liter (Gi/L)
Standard Deviation 1.97999
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Extension W156
|
-0.1712 Giga/Liter (Gi/L)
Standard Deviation NA
Not calculated
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Withdrawal
|
0.3246 Giga/Liter (Gi/L)
Standard Deviation 0.72222
|
|
Change in Neutrophil Count From Baseline in the Absence of Granulocyte-colony Stimulating Factor (G-CSF) Over Time
Last Assessment On-Therapy
|
0.4307 Giga/Liter (Gi/L)
Standard Deviation 1.22084
|
SECONDARY outcome
Timeframe: Week 13Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The frequency and percentage were calculated with 95% confidence interval (CI) of responses (which meet each response criteria) of platelet count, hemoglobin and neutrophil count at Week 13.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Hematological Response at Week 13 in Terms of the Platelet Count, Hemoglobin Level and Neutrophil Count
|
61.9 Percentage of participants
Interval 38.4 to 81.9
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The duration of haematological response was defined, for subjects who responded at the Week 13 visit, as the number of months from the first date of a response until the first date of a relapse or the date the subject was last assessed. Only subjects with at least 2 response assessments were included in the duration of response assessment. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
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|---|---|
|
Duration of Hematological Response in Participants Who Responded at the Week 13
Hematological Response
|
10.68 Months
Interval 1.64 to 28.32
|
|
Duration of Hematological Response in Participants Who Responded at the Week 13
Platelet/Platelet Transfusion
|
32.62 Months
Interval 32.62 to 32.62
|
|
Duration of Hematological Response in Participants Who Responded at the Week 13
Hemoglobin/RBC Transfusion Response
|
19.19 Months
Interval 5.54 to 28.37
|
|
Duration of Hematological Response in Participants Who Responded at the Week 13
Neutrophils Response
|
3.02 Months
Interval 1.64 to 4.63
|
SECONDARY outcome
Timeframe: Day 1, Day 92 (Week 13), Day 183 (Week 26), Extension W39 and Extension W52Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The amount of blood transfusion (platelets, RBC) were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
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|---|---|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Day 1 (Platelets)
|
600.0 milliliter (mL)
Standard Deviation 309.84
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Day 1 (RBC)
|
1663.2 milliliter (mL)
Standard Deviation 1083.31
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Day 92 (Week 13) (Platelets)
|
400.0 milliliter (mL)
Standard Deviation 438.18
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Day 92 (Week 13) (RBC)
|
1152.9 milliliter (mL)
Standard Deviation 978.59
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Day 183 (Week 26) (Platelets)
|
280.0 milliliter (mL)
Standard Deviation 389.87
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Day 183 (Week 26) (RBC)
|
800.0 milliliter (mL)
Standard Deviation 1131.37
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Extension W39 (Platelets)
|
0.0 milliliter (mL)
Standard Deviation 0.00
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Extension W39 (RBC)
|
300.0 milliliter (mL)
Standard Deviation 848.53
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Extension W52 (Platelets)
|
0.0 milliliter (mL)
Standard Deviation 0.00
|
|
Volume of (Platelet and RBC) Transfusion in Each Period
Extension W52 (RBC)
|
400.0 milliliter (mL)
Standard Deviation 1131.37
|
SECONDARY outcome
Timeframe: Day 1, Day 92 (Week 13), Day 183 (Week 26), Extension W39 and Extension W52Population: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The frequency of blood transfusion (platelets, RBC) were summarized. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Day 1 (Platelets)
|
3.0 Tansfusion
Standard Deviation 1.55
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Day 1 (RBC)
|
4.1 Tansfusion
Standard Deviation 2.51
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Day 92 (Week 13) (Platelets)
|
2.0 Tansfusion
Standard Deviation 2.19
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Day 92 (Week 13) (RBC)
|
2.9 Tansfusion
Standard Deviation 2.41
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Day 183 (Week 26) (Platelets)
|
1.4 Tansfusion
Standard Deviation 1.95
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Day 183 (Week 26) (RBC)
|
1.9 Tansfusion
Standard Deviation 2.64
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Extension W39 (Platelets)
|
0.0 Tansfusion
Standard Deviation 0.00
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Extension W39 (RBC)
|
0.8 Tansfusion
Standard Deviation 2.12
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Extension W52 (Platelets)
|
0.0 Tansfusion
Standard Deviation 0.00
|
|
Frequency of (Platelet and RBC) Transfusion in Each Period
Extension W52 (RBC)
|
0.9 Tansfusion
Standard Deviation 2.47
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The proportion of the participants for whom the amount of blood transfusion (platelets and RBC) is decreased was measured and reported as a percentage. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done. This analysis was performed for the subjects who were baseline transfusion dependent.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Percentage of Participants With Reduced Volume of Transfusion (Platelet and RBC)
Platelet Transfusion Decrease
|
83.3 Percentage of participants
|
|
Percentage of Participants With Reduced Volume of Transfusion (Platelet and RBC)
RBC Transfusion Decrease
|
73.7 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 2.5 yearsPopulation: The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
The proportion of participants for whom blood transfusion (platelets and RBC) became unnecessary was measured and reported as a percentage. The measurements were followed up to Week 26 and thereafter in the extension part (Up to the launch of the product after approval, which will be approximately up to two and a half years). Only descriptive analysis done. This analysis was performed for the subjects who were baseline transfusion dependent.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Percentage of Participants Who Become Transfusion (Platelet and RBC) Independent
Platelet Transfusion Independence
|
66.7 Percentage of participants
|
|
Percentage of Participants Who Become Transfusion (Platelet and RBC) Independent
RBC Transfusion Independence
|
47.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 30 days after last dose of study treatmentPopulation: Safety Analysis Set, all subjects who took at least one dose of study treatment. A subject with multiple adverse events within a primary system organ class was counted only once in the total row. Only descriptive analysis done.
The frequency and percentage of subjects who experienced adverse events (AEs), serious adverse events (SAEs) and deaths by primary system organ class (SOC) and MedDRA preferred term were summarized.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Long-term Safety and Tolerability of Eltrombopag
AEs by Primary SOC (SOC)
|
100 Percentage of participants
|
|
Long-term Safety and Tolerability of Eltrombopag
Grade 1 AEs by Primary SOC (SOC)
|
85.7 Percentage of participants
|
|
Long-term Safety and Tolerability of Eltrombopag
Grade 2 AEs by Primary SOC (SOC)
|
81.0 Percentage of participants
|
|
Long-term Safety and Tolerability of Eltrombopag
Grade 3 AEs by Primary SOC (SOC)
|
42.9 Percentage of participants
|
|
Long-term Safety and Tolerability of Eltrombopag
Grade 4 AEs by Primary SOC (SOC)
|
4.8 Percentage of participants
|
|
Long-term Safety and Tolerability of Eltrombopag
SAEs by Primary System Organ Class (SOC)
|
28.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 30 days after last dose of study treatmentPopulation: Safety Analysis Set, all subjects who took at least one dose of study treatment. A subject with multiple adverse events within a primary system organ class was counted only once in the total row. Only descriptive analysis done.
The measurements were followed up to Week 26 and thereafter in the extension part.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Number of Participants With Bleeding Events and Severity of Bleeding
SAE Bleeding - On Treatment
|
0 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
AE Bleeding - On Treatment
|
11 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
Grade 1 AE Bleeding - On Treatment
|
9 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
Grade 2 AE Bleeding - On Treatment
|
2 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
AE Bleeding - Followup Phase
|
6 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
Grade 1 AE Bleeding - Followup Phase
|
5 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
Grade 2 AE Bleeding - Followup Phase
|
1 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
SAE Bleeding - Followup Phase
|
3 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
Grade 1 SAE Bleeding - Followup Phase
|
2 N° of Participants with Bleeding events
|
|
Number of Participants With Bleeding Events and Severity of Bleeding
Grade 2 SAE Bleeding - Followup Phase
|
1 N° of Participants with Bleeding events
|
SECONDARY outcome
Timeframe: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)Population: Pharmacokinetic Analysis Set (PAS), which consisted of all participants with at least one valid PK concentration value, was considered.
At some study sites, full blood sampling for pharmacokinetic (PK) evaluation of Eltrombopag was performed on Day 14 to calculate Cmax, tmax, AUC(0-t), and AUC(0-tau). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Eltrombopag
|
6410 nanogram per milliliter (ng/mL)
Standard Deviation 4200
|
SECONDARY outcome
Timeframe: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)Population: Pharmacokinetic Analysis Set (PAS), which consisted of all participants with at least one valid PK concentration value, was considered.
At some study sites, full blood sampling for pharmacokinetic (PK) evaluation of Eltrombopag was performed on Day 14 to calculate Cmax, tmax, AUC(0-t), and AUC(0-tau). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Time to Reach the Maximum Plasma Concentration (Tmax) for Eltrombopag
|
2.00 Hour
Interval 1.9 to 7.58
|
SECONDARY outcome
Timeframe: Day 14 at 25 mg QD (-0.05, 0.15, 0.30, 0.45, 1.00, 1.30 and 24.00), at 50,75 and 100 mg QD (pre-dose)Population: Pharmacokinetic Analysis Set (PAS), which consisted of all participants with at least one valid PK concentration value, was considered.
At some study sites, full blood sampling for pharmacokinetic (PK) evaluation of Eltrombopag was performed on Day 14 to calculate Cmax, tmax, AUC(0-t), and AUC(0-tau). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Subject Across All Treatments (AUC 0-t) and Over the Dosing Interval (AUC 0-tau) for Eltrombopag
AUC(0-t)
|
123000 Hours*nanograms/milliliter (hr*ng/mL)
Standard Deviation 92900
|
|
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Subject Across All Treatments (AUC 0-t) and Over the Dosing Interval (AUC 0-tau) for Eltrombopag
AUC(0-tau)
|
99200 Hours*nanograms/milliliter (hr*ng/mL)
Standard Deviation 119000
|
SECONDARY outcome
Timeframe: Day 14 (pre-dose, 1, 2, 4, 6, 8 and 24 post-dose), Day 15 (pre-dose)Population: Pharmacokinetic Analysis Set (PAS), which consisted of all participants with at least one valid PK concentration value, was considered.
At every study center, blood samples was be collected on Day 15 of multiple doses of eltrombopag 25 mg to determine the plasma eltrombopag concentration prior to the next dose (trough concentration). In addition, one-point pre-dose blood sampling was performed at every study center on Day 15 of multiple doses of eltrombopag 50 mg, 75 mg and 100 mg to determine trough concentrations. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Outcome measures
| Measure |
Eltrombopag
n=21 Participants
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 0Hr
|
4530 nanogram per milliliter (ng/mL)
Standard Deviation 3870
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 1Hr
|
5240 nanogram per milliliter (ng/mL)
Standard Deviation 3740
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 2Hr
|
5980 nanogram per milliliter (ng/mL)
Standard Deviation 3990
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 4Hr
|
5870 nanogram per milliliter (ng/mL)
Standard Deviation 3870
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 6Hr
|
5720 nanogram per milliliter (ng/mL)
Standard Deviation 4130
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 8Hr
|
5430 nanogram per milliliter (ng/mL)
Standard Deviation 4170
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 14) - 24Hr
|
4390 nanogram per milliliter (ng/mL)
Standard Deviation 3680
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 25 mg (Day 15) - 0Hr
|
3730 nanogram per milliliter (ng/mL)
Standard Deviation 2430
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 50 mg (Day 15) - 0Hr
|
8530 nanogram per milliliter (ng/mL)
Standard Deviation 6410
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 75 mg (Day 15) - 0Hr
|
15200 nanogram per milliliter (ng/mL)
Standard Deviation 12000
|
|
Mean Change in Eltrombopag Concentration in Pharmacokinetic Serum Samples Over Time at Days 14 and 15
Eltrombopag 100 mg (Day 15) - 0Hr
|
19300 nanogram per milliliter (ng/mL)
Standard Deviation 15000
|
Adverse Events
Eltrombopag
Serious adverse events
| Measure |
Eltrombopag
n=21 participants at risk
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Eye disorders
Retinal detachment
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Enterocolitis
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Investigations
Fibrin D dimer increased
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
4.8%
1/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
Other adverse events
| Measure |
Eltrombopag
n=21 participants at risk
Subjects were assigned the investigational product (eltrombopag 25 mg/day) orally once a day under fasting condition. The dose adjustment was done every 2 weeks according to the platelet count (increased by eltrombopag 25 mg/day every 2 weeks according to the platelet count up to 100 mg/day).
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
19.0%
4/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Diarrhoea
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Dyspepsia
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Nausea
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Gastrointestinal disorders
Periodontal disease
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
General disorders
Pyrexia
|
14.3%
3/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
19.0%
4/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Infections and infestations
Gastroenteritis
|
14.3%
3/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Infections and infestations
Influenza
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Infections and infestations
Nasopharyngitis
|
38.1%
8/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Injury, poisoning and procedural complications
Allergic transfusion reaction
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Investigations
Blood alkaline phosphatase increased
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Investigations
Blood bilirubin increased
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Investigations
Blood creatinine increased
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Nervous system disorders
Headache
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.5%
2/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
14.3%
3/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
|
Vascular disorders
Hypertension
|
14.3%
3/21 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3 years and 1 month.
|
Additional Information
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 (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER