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Trial Outcomes & Findings for Eltrombopag Combined With Cyclosporine as First Line Therapy in Patients With Severe Acquired Aplastic Anemia (NCT NCT02998645)

NCT ID: NCT02998645

Last Updated: 2023-12-11

Results Overview

Overall hematologic response rate by 6 months was defined as the percentage of participants with complete response (CR) or partial response (PR) any time on or before 6 months. PR was defined as any two of the following parameters at two consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * Absolute neutrophil count (ANC) \>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL CR was defined as all three parameters meet the following criteria at two consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \> 1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2023-12-11

Participant Flow

The study was conducted across 20 centers in 9 countries.

Participants received a combination of eltrombopag and cyclosporine for 6 months (Treatment period 1). Participants who were responders at 6 months were followed-up for cyclosporine tapering until relapse or Month 24 whichever was earlier (Treatment period 2)

Participant milestones

Participant milestones
Measure
Eltrombopag + Cyclosporine
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Treatment Period 1
STARTED
54
Treatment Period 1
East/Southeast Asian Ethnicity
18
Treatment Period 1
Non-East/Southeast Asian Ethnicity
36
Treatment Period 1
COMPLETED
35
Treatment Period 1
NOT COMPLETED
19
Treatment Period 2
STARTED
21
Treatment Period 2
COMPLETED
11
Treatment Period 2
NOT COMPLETED
10

Reasons for withdrawal

Reasons for withdrawal
Measure
Eltrombopag + Cyclosporine
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Treatment Period 1
Adverse Event
6
Treatment Period 1
Death
5
Treatment Period 1
Technical Problems
4
Treatment Period 1
Lack of Efficacy
2
Treatment Period 1
Progressive disease
1
Treatment Period 1
Subject/guardian decision
1
Treatment Period 2
Lack of Efficacy
5
Treatment Period 2
Adverse Event
2
Treatment Period 2
Progressive disease
2
Treatment Period 2
Physician Decision
1

Baseline Characteristics

Eltrombopag Combined With Cyclosporine as First Line Therapy in Patients With Severe Acquired Aplastic Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Age, Continuous
52.0 Years
STANDARD_DEVIATION 17.88 • n=39 Participants
Sex: Female, Male
Female
20 Participants
n=39 Participants
Sex: Female, Male
Male
34 Participants
n=39 Participants
Race/Ethnicity, Customized
Hispanic or Latino
22 Participants
n=39 Participants
Race/Ethnicity, Customized
Southeast Asian
11 Participants
n=39 Participants
Race/Ethnicity, Customized
East Asian
7 Participants
n=39 Participants
Race/Ethnicity, Customized
West Asian
5 Participants
n=39 Participants
Race/Ethnicity, Customized
Other
4 Participants
n=39 Participants
Race/Ethnicity, Customized
South Asian
3 Participants
n=39 Participants
Race/Ethnicity, Customized
Mixed ethnicity
1 Participants
n=39 Participants
Race/Ethnicity, Customized
Not reported
1 Participants
n=39 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: Full Analysis Set (FAS) including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine).

Overall hematologic response rate by 6 months was defined as the percentage of participants with complete response (CR) or partial response (PR) any time on or before 6 months. PR was defined as any two of the following parameters at two consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * Absolute neutrophil count (ANC) \>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL CR was defined as all three parameters meet the following criteria at two consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \> 1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Overall Hematologic Response Rate by 6 Months
46.3 Percentage of participants
Interval 32.6 to 60.4

SECONDARY outcome

Timeframe: Up to 3 months

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine).

Overall hematologic response rate by 3 months was defined as the percentage of participants with CR or PR any time on or before 3 months. PR was defined as any two of the following parameters at two consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * ANC \>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL CR was defined as all three parameters meet the following criteria at two consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \> 1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Overall Hematologic Response Rate by 3 Months
40.7 Percentage of participants
Interval 27.6 to 55.0

SECONDARY outcome

Timeframe: 12 and 24 months

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine).

Overall hematologic response rate at 12 and 24 months was defined as the percentage of participants with CR or PR at 12 and 24 months respectively. PR was defined as any two of the following parameters at two consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * ANC\>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL CR was defined as all three parameters meet the following criteria at two consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \> 1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Overall Hematologic Response Rate at 12 and 24 Months
At 12 months
18.5 Percentage of participants
Interval 9.3 to 31.4
Overall Hematologic Response Rate at 12 and 24 Months
At 24 months
18.5 Percentage of participants
Interval 9.3 to 31.4

SECONDARY outcome

Timeframe: Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Population: All participants in the FAS who achieved hematologic response (either CR or PR) any time on or before the 6 months visit

Duration of first hematologic response is the time from the date of the start of first response to the date of first relapse. Relapse is defined as no longer meeting definition of PR or CR. Kaplan-Meier method was used for the analysis. If no relapse occurred, the participant was censored at the date of last contact. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24. PR was defined as any 2 of the following parameters at 2 consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * ANC \>500/μL * Platelet count \>20 000/μL * Reticulocyte count \>60 000/μL. CR was defined as all 3 parameters meet the following criteria at 2 consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC \>1 000/μL * Platelet count \>100 000/μL * Hemoglobin \>10 g/L

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=25 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Duration of First Hematologic Response
351.0 Days
Interval 99.0 to
NA: Not estimable due to the low number of participants with events

SECONDARY outcome

Timeframe: Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Population: All participants in the FAS who achieved hematologic response (either CR or PR) any time on or before the 6 months visit

Relapse was defined as no longer meeting the definition of PR (and not CR). Relapse rate by 6 months and 24 was defined as the percentage of responders by 6 months who relapsed prior to 6 months or prior to 24 months respectively. Responders by 6 months were participants who achieved CR or PR any time on or before 6 months. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24. PR: any 2 of the following parameters at 2 consecutive measurements at least 7 days apart and no platelet transfusion within 7 days of platelet measurement: * ANC\>500/μL * Platelet count\>20 000/μL * Reticulocyte count\>60 000/μL. CR: all 3 parameters meet the following criteria at 2 consecutive measurements at least 7 days apart and no platelet transfusions within 7 days of platelet measurement and no red blood cell transfusion with 14 days of the hemoglobin measurements: * ANC\>1 000/μL * Platelet count\>100 000/μL * Hemoglobin\>10 g/L

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=25 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Relapse Rate by 6 and 24 Months
By 6 months
32.0 Percentage of participants
Interval 14.9 to 53.5
Relapse Rate by 6 and 24 Months
By 24 months
44.0 Percentage of participants
Interval 24.4 to 65.1

SECONDARY outcome

Timeframe: Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine).

The percentage of participants with evolution to myelodysplasia, PNH and acute leukemia occurring at any time during the study. Clonal evolution to myelodysplasia was defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Clonal evolution to leukemia was defined as greater than 20% peripheral blood and/or marrow blasts. Clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH) was defined as a clone at baseline \< 10% that rose to greater than 50% on study. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Percentage of Participants With Evolution to Myelodysplasia, Paroxysmal Nocturnal Hemoglobinuria (PNH) and Leukemia
0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine).

Percentage of participants who were RBC transfusion independent at least once by 6 months and by 24 months (responders only). Independence was defined as no RBC transfusion for at least 56 days. Results are presented for responders and non-responders. If any participant achieved hematologic response (either CR or PR) any time on or before 6 months, they were considered as responders, else they were considered as non-responders. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Percentage of Participants Who Were Red Blood Cells (RBC) Transfusion Independent
Day 1 to 6 months- Responders
17 Participants
Percentage of Participants Who Were Red Blood Cells (RBC) Transfusion Independent
Day 1 to 24 months- Responders
20 Participants
Percentage of Participants Who Were Red Blood Cells (RBC) Transfusion Independent
Day 1 to 6 months- Non-Responders
5 Participants

SECONDARY outcome

Timeframe: Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine).

Percentage of participants who were platelet transfusion independent at least once by 6 months and by 24 months (responders only). Independence was defined as no platelet transfusion for at least 28 days. Results are presented for responders and non-responders. If any participant achieved hematologic response (either CR or PR) any time on or before 6 months, they were considered as responders, else they were considered as non-responders. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Percentage of Participants Who Were Platelet Transfusion Independent
Day 1 to 6 months- Responders
25 Participants
Percentage of Participants Who Were Platelet Transfusion Independent
Day 1 to 24 months- Responders
25 Participants
Percentage of Participants Who Were Platelet Transfusion Independent
Day 1 to 6 months- Non-responders
13 Participants

SECONDARY outcome

Timeframe: Up to 6 months (non-responders at Month 6) and up to 24 months (responders at Month 6)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine)

Longest duration of transfusion independence (platelet or RBC) by 6 months and by 24 months (responders only). Transfusion independence was defined as no transfusions required in at least a 28-day period for platelet transfusion and at least 56-day period for RBC transfusion. The duration of the longest interval with transfusion independence was summarized using Kaplan-Meier analysis. Results are presented for responders and non-responders. If any participant achieved hematologic response (either CR or PR) any time on or before 6 months, they were considered as responders, else they were considered as non-responders. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Longest Duration of Transfusion Independence (Platelet or RBC)
Day 1 to 6 months- Responders
NA Days
NA: not estimable due to the low number of participants with events
Longest Duration of Transfusion Independence (Platelet or RBC)
Day 1 to 24 months- Responders
NA Days
Interval 498.0 to
NA: not estimable due to the low number of participants with events
Longest Duration of Transfusion Independence (Platelet or RBC)
Day 1 to 6 months- Non-Responders
87.0 Days
Interval 48.0 to
NA: not estimable due to the low number of participants with events

SECONDARY outcome

Timeframe: Baseline, every 2 weeks from Week 2 to Week 24 or End of Treatment Period 1 (for all participants); and at Week 38, Week 53, Month 24 or End of Treatment Period 2 (for responders at Month 6 only)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine). Only participants with an evaluable baseline visit and at least one evaluable post-baseline visit were included in the analysis. Number analyzed are the number of participants with data available for analysis at the given category.

The FACT-G consists of 27-items divided into 4 domains (physical well-being, social well-being, emotional and functional well-being). All items of the FACT-G use a 5 point scale ranging from 0 to 4 with a 0 rating being "not at all" and a 4 rating being "very much". Total FACT-G score is the sum of physical well-being score, social well-being score, emotional well-being score and functional well-being score. Score ranges from 0 to 108, with higher scores indicating better quality of life (QoL). A positive change from baseline indicates improvement in the QoL. Results are presented for responders and non-responders. If any participant achieved hematologic response (either CR or PR) any time on or before 6 months, they were considered as responders, else they were considered as non-responders. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 2 (Treatment period 1) - Responders
-2.0 Score on a scale
Interval -26.0 to 30.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 4 (Treatment period 1) - Responders
-3.0 Score on a scale
Interval -22.0 to 23.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 6 (Treatment period 1) - Responders
-0.3 Score on a scale
Interval -48.0 to 30.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 8 (Treatment period 1) - Responders
0.0 Score on a scale
Interval -25.0 to 30.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 10 (Treatment period 1) - Responders
-1.3 Score on a scale
Interval -43.0 to 33.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 12 (Treatment period 1) - Responders
0.8 Score on a scale
Interval -40.0 to 30.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 14 (Treatment period 1) - Responders
1.0 Score on a scale
Interval -44.0 to 29.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 16 (Treatment period 1) - Responders
-2.0 Score on a scale
Interval -51.0 to 35.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 18 (Treatment period 1) - Responders
3.0 Score on a scale
Interval -41.0 to 37.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 20 (Treatment period 1) - Responders
-1.0 Score on a scale
Interval -46.0 to 41.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 22 (Treatment period 1) - Responders
1.0 Score on a scale
Interval -43.0 to 39.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 24 (Treatment period 1) - Responders
1.8 Score on a scale
Interval -46.0 to 35.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 26 (Treatment period 1) - Responders
1.0 Score on a scale
Interval -51.0 to 38.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
End of treatment period 1 - Responders
-1.0 Score on a scale
Interval -51.0 to 38.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 38 (Treatment period 2)- Responders
5.7 Score on a scale
Interval -43.0 to 47.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 53 (Treatment period 2)- Responders
4.0 Score on a scale
Interval -46.0 to 42.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Month 24 (Treatment period 2)- Responders
22.0 Score on a scale
Interval -50.0 to 84.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
End of treatment period 2 - Responders
13.5 Score on a scale
Interval -5.0 to 47.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 2 (Treatment period 1) - Non-Responders
-0.3 Score on a scale
Interval -34.0 to 21.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 4 (Treatment period 1) - Non-Responders
-1.0 Score on a scale
Interval -42.0 to 22.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 6 (Treatment period 1) - Non-Responders
-3.6 Score on a scale
Interval -45.0 to 17.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 8 (Treatment period 1) - Non-Responders
1.5 Score on a scale
Interval -36.0 to 99.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 10 (Treatment period 1) - Non-Responders
-0.9 Score on a scale
Interval -27.0 to 25.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 12 (Treatment period 1) - Non-Responders
-0.3 Score on a scale
Interval -54.0 to 26.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 14 (Treatment period 1) - Non-Responders
-0.3 Score on a scale
Interval -39.0 to 28.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 16 (Treatment period 1) - Non-Responders
0.3 Score on a scale
Interval -50.0 to 23.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 18 (Treatment period 1) - Non-Responders
-2.6 Score on a scale
Interval -45.0 to 19.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 20 (Treatment period 1) - Non-Responders
-1.5 Score on a scale
Interval -44.0 to 22.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 22 (Treatment period 1) - Non-Responders
-1.0 Score on a scale
Interval -45.0 to 12.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 24 (Treatment period 1) - Non-Responders
2.7 Score on a scale
Interval -30.0 to 18.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
Week 26 (Treatment period 1) - Non-Responders
-2.7 Score on a scale
Interval -25.0 to 24.0
Change From Baseline in Scores of Functional Assessment of Cancer Therapy - General (FACT-G) Patient Reported Outcome
End of treatment period 1 - Non-Responders
-2.0 Score on a scale
Interval -30.0 to 24.0

SECONDARY outcome

Timeframe: Baseline, every 2 weeks from Week 2 to Week 24 or End of Treatment Period 1 (for all participants); and at Week 38, Week 53, Month 24 or End of Treatment Period 2 (for responders at Month 6 only)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine). Only participants with an evaluable baseline visit and at least one evaluable post-baseline visit were included in the analysis. Number analyzed are the number of participants with data available for analysis at the given category.

The FACT-TH18 is comprised of FACT-G and a thrombocytopenia specific questionnaire. FACT-G consists of 27-items divided into 4 domains (physical, social, emotional and functional well-being). FACT-TH18 has 18 additional items which asks the patient to rate degree of thrombocytopenia. All items of the FACT-TH18 use a 5 point scale ranging from 0 to 4, with 0 = "not at all" and 4 = "very much". Total FACT-TH18 score is the sum of physical, social, emotional and functional well-being scores, and thrombocytopenia subscale. Score ranges from 0 to 180, with higher scores indicating better QoL. A positive change from baseline indicates improvement in the QoL. Results are presented for responders and non-responders. If any participant achieved hematologic response (CR or PR) any time on or before 6 months, they were considered as responders, else they were considered as non-responders. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 2 (Treatment period 1) - Responders
2.3 Score on a scale
Interval -43.0 to 43.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 4 (Treatment period 1) - Responders
-1.5 Score on a scale
Interval -37.0 to 54.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 6 (Treatment period 1) - Responders
8.4 Score on a scale
Interval -62.0 to 70.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 8 (Treatment period 1) - Responders
9.0 Score on a scale
Interval -34.0 to 66.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 10 (Treatment period 1) - Responders
3.4 Score on a scale
Interval -44.0 to 73.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 12 (Treatment period 1) - Responders
9.3 Score on a scale
Interval -45.0 to 69.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 14 (Treatment period 1) - Responders
6.4 Score on a scale
Interval -45.0 to 63.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 16 (Treatment period 1) - Responders
7.8 Score on a scale
Interval -47.0 to 68.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 18 (Treatment period 1) - Responders
13.9 Score on a scale
Interval -46.0 to 77.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 20 (Treatment period 1) - Responders
11.8 Score on a scale
Interval -48.0 to 81.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 22 (Treatment period 1) - Responders
13.5 Score on a scale
Interval -46.0 to 81.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 24 (Treatment period 1) - Responders
14.5 Score on a scale
Interval -48.0 to 72.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 26 (Treatment period 1) - Responders
18.2 Score on a scale
Interval -57.0 to 72.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
End of treatment period 1 - Responders
13.9 Score on a scale
Interval -57.0 to 72.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 38 (Treatment period 2)- Responders
21.7 Score on a scale
Interval -50.0 to 88.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 53 (Treatment period 2)- Responders
22.0 Score on a scale
Interval -50.0 to 84.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Month 24 (Treatment period 2)- Responders
35.7 Score on a scale
Interval 5.0 to 95.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
End of treatment period 2 - Responders
6.9 Score on a scale
Interval -55.0 to 35.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 2 (Treatment period 1) - Non-Responders
0.6 Score on a scale
Interval -78.0 to 39.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 4 (Treatment period 1) - Non-Responders
2.1 Score on a scale
Interval -77.0 to 45.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 6 (Treatment period 1) - Non-Responders
-1.5 Score on a scale
Interval -97.0 to 42.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 8 (Treatment period 1) - Non-Responders
2.0 Score on a scale
Interval -54.0 to 43.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 10 (Treatment period 1) - Non-Responders
5.2 Score on a scale
Interval -22.0 to 41.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 12 (Treatment period 1) - Non-Responders
1.8 Score on a scale
Interval -101.0 to 49.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 14 (Treatment period 1) - Non-Responders
2.8 Score on a scale
Interval -64.0 to 41.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 16 (Treatment period 1) - Non-Responders
2.1 Score on a scale
Interval -98.0 to 38.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 18 (Treatment period 1) - Non-Responders
0.5 Score on a scale
Interval -78.0 to 27.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 20 (Treatment period 1) - Non-Responders
2.4 Score on a scale
Interval -68.0 to 43.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 22 (Treatment period 1) - Non-Responders
-1.3 Score on a scale
Interval -67.0 to 39.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 24 (Treatment period 1) - Non-Responders
0.7 Score on a scale
Interval -31.0 to 43.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
Week 26 (Treatment period 1) - Non-Responders
-1.4 Score on a scale
Interval -24.0 to 41.0
Change From Baseline in Scores of FACT - Thrombocytopenia 18 (FACT-TH18) Patient Reported Outcome
End of treatment period 1 - Non-Responders
-1.4 Score on a scale
Interval -27.0 to 41.0

SECONDARY outcome

Timeframe: Baseline, every 2 weeks from Week 2 to Week 24 or End of Treatment Period 1 (for all participants); and at Week 38, Week 53, Month 24 or End of Treatment Period 2 (for responders at Month 6 only)

Population: FAS including all subjects who received at least one dose of study treatment (eltrombopag or cyclosporine). Only participants with an evaluable baseline visit and at least one evaluable post-baseline visit were included in the analysis. Number analyzed are the number of participants with data available for analysis at the given category.

The FACIT- Fatigue is a 13-item fatigue subscale that asks the patient to rate their degree of tiredness, weakness and fatigue. All items of the FACIT-Fatigue use a 5-point scale ranging from 0 to 4 with a 0 rating being "not at all" and a 4 rating being "very much". Total score ranges from 0 to 52. Negatively worded items were reverse scored before summing so that higher total scores indicate less fatigue. A positive change from baseline indicates improvement. Results are presented for responders and non-responders. If any participant achieved hematologic response (either CR or PR) any time on or before 6 months, they were considered as responders, else they were considered as non-responders. Only participants who achieved hematologic response of CR or PR at Month 6 were followed up until Month 24.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=54 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 2 (Treatment period 1) - Responders
3.0 Score on a scale
Interval -13.0 to 34.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 4 (Treatment period 1) - Responders
2.0 Score on a scale
Interval -16.0 to 22.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 6 (Treatment period 1) - Responders
4.0 Score on a scale
Interval -22.0 to 32.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 8 (Treatment period 1) - Responders
6.0 Score on a scale
Interval -7.0 to 29.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 10 (Treatment period 1) - Responders
4.5 Score on a scale
Interval -11.0 to 30.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 12 (Treatment period 1) - Responders
5.5 Score on a scale
Interval -11.0 to 31.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 14 (Treatment period 1) - Responders
6.5 Score on a scale
Interval -5.0 to 26.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 16 (Treatment period 1) - Responders
6.0 Score on a scale
Interval -5.0 to 28.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 18 (Treatment period 1) - Responders
7.0 Score on a scale
Interval -5.0 to 28.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 20 (Treatment period 1) - Responders
6.0 Score on a scale
Interval -5.0 to 29.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 22 (Treatment period 1) - Responders
6.0 Score on a scale
Interval -8.0 to 33.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 24 (Treatment period 1) - Responders
6.0 Score on a scale
Interval -5.0 to 29.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 26 (Treatment period 1) - Responders
7.0 Score on a scale
Interval -9.0 to 32.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
End of treatment period 1 - Responders
6.0 Score on a scale
Interval -9.0 to 32.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 38 (Treatment period 2)- Responders
6.0 Score on a scale
Interval -8.0 to 33.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 53 (Treatment period 2)- Responders
8.0 Score on a scale
Interval -2.0 to 41.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Month 24 (Treatment period 2)- Responders
9.0 Score on a scale
Interval 1.0 to 31.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
End of treatment period 2 - Responders
11.5 Score on a scale
Interval -5.0 to 42.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 2 (Treatment period 1) - Non-Responders
-0.5 Score on a scale
Interval -23.0 to 19.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 4 (Treatment period 1) - Non-Responders
-2.0 Score on a scale
Interval -38.0 to 20.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 6 (Treatment period 1) - Non-Responders
0.0 Score on a scale
Interval -43.0 to 18.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 8 (Treatment period 1) - Non-Responders
-1.0 Score on a scale
Interval -27.0 to 14.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 10 (Treatment period 1) - Non-Responders
0.5 Score on a scale
Interval -25.0 to 16.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 12 (Treatment period 1) - Non-Responders
-1.0 Score on a scale
Interval -42.0 to 15.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 14 (Treatment period 1) - Non-Responders
-1.5 Score on a scale
Interval -43.0 to 16.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 16 (Treatment period 1) - Non-Responders
-0.5 Score on a scale
Interval -46.0 to 15.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 18 (Treatment period 1) - Non-Responders
-6.0 Score on a scale
Interval -43.0 to 15.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 20 (Treatment period 1) - Non-Responders
-6.0 Score on a scale
Interval -45.0 to 22.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 22 (Treatment period 1) - Non-Responders
-4.0 Score on a scale
Interval -45.0 to 15.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 24 (Treatment period 1) - Non-Responders
-7.0 Score on a scale
Interval -19.0 to 12.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
Week 26 (Treatment period 1) - Non-Responders
-8.0 Score on a scale
Interval -19.0 to 15.0
Change From Baseline in Scores of Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT- Fatigue) Patient Reported Outcome
End of treatment period 1 - Non-Responders
-4.0 Score on a scale
Interval -19.0 to 15.0

SECONDARY outcome

Timeframe: Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose.

Population: Participants in the Pharmacokinetic Analysis Set (PAS) including participants who provided at least one evaluable PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

Cmax is the observed maximum plasma concentration following administration. The plasma samples from all participants were assayed for eltrombopag concentrations using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS). The lower limit of quantitation (LLOQ) was 0.1 microgram/milliliter (ug/mL). Concentration values below the LLOQ were reported as zero, and missing samples were labeled accordingly. Results are reported by ethnicity: East/Southeast Asian participants received eltrombopag planned dose of 100mg/day and all other participants received eltrombopag planned dose of 150mg/day.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=44 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Pharmacokinetic Parameter- Cmax of Eltrombopag When Combined With Cyclosporine
East/Southeast Asian ethnicity
29.1 microgram/milliliter (ug/mL)
Geometric Coefficient of Variation 43.5
Pharmacokinetic Parameter- Cmax of Eltrombopag When Combined With Cyclosporine
Non-East/Southeast Asian ethnicity
38.7 microgram/milliliter (ug/mL)
Geometric Coefficient of Variation 38.0

SECONDARY outcome

Timeframe: Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose

Population: Participants in the Pharmacokinetic Analysis Set (PAS) including participants who provided at least one evaluable PK concentration. Only participants with an evaluable PK parameter (Cmax) were included in the analysis.

AUClast is the area under the curve calculated to the last quantifiable concentration point (Tlast). The plasma samples from all participants were assayed for eltrombopag concentrations using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS). The lower limit of quantitation (LLOQ) was 0.1 ug/mL. Concentration values below the LLOQ were reported as zero, and missing samples were labeled accordingly. Results are reported by ethnicity: East/Southeast Asian participants received eltrombopag planned dose of 100mg/day and all other participants received eltrombopag planned dose of 150mg/day.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=44 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Pharmacokinetic Parameter-AUClast of Eltrombopag When Combined With Cyclosporine
East/Southeast Asian ethnicity
583 hour*microgram/milliliter (h*ug/mL)
Geometric Coefficient of Variation 38.3
Pharmacokinetic Parameter-AUClast of Eltrombopag When Combined With Cyclosporine
Non-East/Southeast Asian ethnicity
702 hour*microgram/milliliter (h*ug/mL)
Geometric Coefficient of Variation 59.9

SECONDARY outcome

Timeframe: Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose

Population: Participants in the Pharmacokinetic Analysis Set (PAS) including participants who provided at least one evaluable PK concentration. Only participants with an evaluable PK parameter (AUCtau) were included in the analysis.

AUCtau is the area under the curve calculated to the end of the dosing interval (tau). The plasma samples from all participants were assayed for eltrombopag concentrations using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS). The lower limit of quantitation (LLOQ) was 0.1 ug/mL. Concentration values below the LLOQ were reported as zero, and missing samples were labeled accordingly. Results are reported by ethnicity: East/Southeast Asian participants received eltrombopag planned dose of 100mg/day and all other participants received eltrombopag planned dose of 150mg/day.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=18 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Pharmacokinetic Parameter- AUCtau of Eltrombopag When Combined With Cyclosporine
East/Southeast Asian ethnicity
686 hour*microgram/milliliter (h*ug/mL)
Geometric Coefficient of Variation 32.4
Pharmacokinetic Parameter- AUCtau of Eltrombopag When Combined With Cyclosporine
Non-East/Southeast Asian ethnicity
727 hour*microgram/milliliter (h*ug/mL)
Geometric Coefficient of Variation 33.0

SECONDARY outcome

Timeframe: Week 2 at pre-dose

Population: Participants in the Pharmacokinetic Analysis Set (PAS) including participants who provided at least one evaluable PK concentration. Only participants with an evaluable PK parameter (Ctrough) were included in the analysis.

Ctrough is the pre-dose plasma concentration. The plasma samples from all participants were assayed for eltrombopag concentrations using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS). The lower limit of quantitation (LLOQ) was 0.1 ug/mL. Concentration values below the LLOQ were reported as zero, and missing samples were labeled accordingly. Results are reported by ethnicity: East/Southeast Asian participants received eltrombopag planned dose of 100mg/day and all other participants received eltrombopag planned dose of 150mg/day.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=45 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Pharmacokinetic Parameter- Ctrough of Eltrombopag When Combined With Cyclosporine
East/Southeast Asian ethnicity
19.3 microgram/milliliter (ug/mL)
Geometric Coefficient of Variation 45.3
Pharmacokinetic Parameter- Ctrough of Eltrombopag When Combined With Cyclosporine
Non-East/Southeast Asian ethnicity
27.2 microgram/milliliter (ug/mL)
Geometric Coefficient of Variation 44.1

SECONDARY outcome

Timeframe: Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose

Population: Participants in the Pharmacokinetic Analysis Set (PAS) including participants who provided at least one evaluable PK concentration. Only participants with an evaluable PK parameter (Tmax) were included in the analysis.

Tmax is the time to reach peak or maximum concentration. The plasma samples from all participants were assayed for eltrombopag concentrations using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS). The lower limit of quantitation (LLOQ) was 0.1 ug/mL. Concentration values below the LLOQ were reported as zero, and missing samples were labeled accordingly. Results are reported by ethnicity: East/Southeast Asian participants received eltrombopag planned dose of 100mg/day and all other participants received eltrombopag planned dose of 150mg/day.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=44 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Pharmacokinetic Parameter- Tmax of Eltrombopag When Combined With Cyclosporine
East/Southeast Asian ethnicity
5.79 Hours
Interval 1.93 to 8.0
Pharmacokinetic Parameter- Tmax of Eltrombopag When Combined With Cyclosporine
Non-East/Southeast Asian ethnicity
3.75 Hours
Interval 0.0 to 8.0

SECONDARY outcome

Timeframe: Week 2 at pre-dose and 2, 4, 6 and 8 hours post-dose

Population: Participants in the Pharmacokinetic Analysis Set (PAS) including participants who provided at least one evaluable PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

CLss/F is the apparent systemic (or total body) clearance at steady state from plasma. The plasma samples from all participants were assayed for eltrombopag concentrations using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS). The lower limit of quantitation (LLOQ) was 0.1 ug/mL. Concentration values below the LLOQ were reported as zero, and missing samples were labeled accordingly. Results are reported by ethnicity: East/Southeast Asian participants received eltrombopag planned dose of 100mg/day and all other participants received eltrombopag planned dose of 150mg/day.

Outcome measures

Outcome measures
Measure
Eltrombopag + Cyclosporine
n=18 Participants
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Pharmacokinetic Parameter- CLss/F of Eltrombopag When Combined With Cyclosporine
East/Southeast Asian ethnicity
146 milliliter/hour (mL/h)
Geometric Coefficient of Variation 32.4
Pharmacokinetic Parameter- CLss/F of Eltrombopag When Combined With Cyclosporine
Non-East/Southeast Asian ethnicity
206 milliliter/hour (mL/h)
Geometric Coefficient of Variation 33.0

Adverse Events

Eltrombopag + Cyclosporine

Serious events: 27 serious events
Other events: 47 other events
Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure
Eltrombopag + Cyclosporine
n=54 participants at risk
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Blood and lymphatic system disorders
Febrile neutropenia
18.5%
10/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Cardiac disorders
Cardiac arrest
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Dental caries
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Gastric dysplasia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Haematochezia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Intestinal haemorrhage
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Oral pain
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Asthenia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Fatigue
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
General physical health deterioration
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Multiple organ dysfunction syndrome
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Pyrexia
3.7%
2/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Hepatobiliary disorders
Drug-induced liver injury
3.7%
2/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
COVID-19
3.7%
2/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
COVID-19 pneumonia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Cellulitis
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Erysipelas
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Escherichia sepsis
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Infection
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Pneumonia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Pneumonia fungal
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Prostatic abscess
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Sepsis
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Septic shock
3.7%
2/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Tonsillitis
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Urinary tract infection
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Urosepsis
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Viral upper respiratory tract infection
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Injury, poisoning and procedural complications
Incisional hernia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Blood creatinine increased
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hyperkalaemia
3.7%
2/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hyponatraemia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Psychiatric disorders
Depression
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Renal and urinary disorders
Acute kidney injury
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Respiratory, thoracic and mediastinal disorders
Dyspnoea
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Respiratory, thoracic and mediastinal disorders
Respiratory failure
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Skin and subcutaneous tissue disorders
Rash maculo-papular
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Vascular disorders
Thrombosis
1.9%
1/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months

Other adverse events

Other adverse events
Measure
Eltrombopag + Cyclosporine
n=54 participants at risk
Participants received eltrombopag (orally, 100 mg once daily for East/Southeast Asian participants / 150 mg once daily for all other participants) in combination with cyclosporine (orally, 10.0 mg/kg/day in divided doses every 12 hours) for up to 6 months. Thereafter, responders at Month 6 were treated with cyclosporine until Month 24
Cardiac disorders
Palpitations
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Eye disorders
Retinal haemorrhage
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Abdominal pain
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Abdominal pain upper
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Constipation
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Diarrhoea
22.2%
12/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Dyspepsia
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Gastritis
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Gingival bleeding
13.0%
7/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Gingival hypertrophy
11.1%
6/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Mouth haemorrhage
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Mouth ulceration
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Nausea
29.6%
16/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Odynophagia
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Gastrointestinal disorders
Vomiting
20.4%
11/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Asthenia
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Oedema peripheral
14.8%
8/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
General disorders
Pyrexia
14.8%
8/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Nasopharyngitis
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Oral candidiasis
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Oral herpes
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Infections and infestations
Upper respiratory tract infection
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Injury, poisoning and procedural complications
Contusion
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Injury, poisoning and procedural complications
Procedural pain
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Alanine aminotransferase increased
22.2%
12/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Aspartate aminotransferase increased
18.5%
10/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Blood alkaline phosphatase increased
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Blood bilirubin increased
40.7%
22/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Blood creatinine increased
18.5%
10/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
Neutrophil count decreased
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Investigations
SARS-CoV-2 test positive
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hypercholesterolaemia
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hyperglycaemia
11.1%
6/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hyperkalaemia
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hypertriglyceridaemia
13.0%
7/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hyperuricaemia
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hypokalaemia
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Hypomagnesaemia
18.5%
10/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Metabolism and nutrition disorders
Iron overload
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Musculoskeletal and connective tissue disorders
Arthralgia
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Musculoskeletal and connective tissue disorders
Back pain
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Musculoskeletal and connective tissue disorders
Muscle spasms
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Musculoskeletal and connective tissue disorders
Myalgia
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Nervous system disorders
Dizziness
11.1%
6/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Nervous system disorders
Headache
18.5%
10/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Nervous system disorders
Tremor
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Respiratory, thoracic and mediastinal disorders
Cough
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Respiratory, thoracic and mediastinal disorders
Dyspnoea
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Skin and subcutaneous tissue disorders
Ecchymosis
5.6%
3/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Skin and subcutaneous tissue disorders
Petechiae
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Skin and subcutaneous tissue disorders
Pruritus
7.4%
4/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Skin and subcutaneous tissue disorders
Rash
9.3%
5/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months
Vascular disorders
Hypertension
14.8%
8/54 • From day of first dose of study medication to 30 days after last dose of study medication, assessed up to 25 months

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 (ie, data from all sites) in the clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER