Trial Outcomes & Findings for Eltrombopag and the Bcl-extra-large (xL) Pathway in Idiopathic Thrombocytopenic Purpura (ITP) (NCT NCT00902018)
NCT ID: NCT00902018
Last Updated: 2019-03-18
Results Overview
number of patients in whom Platelet Counts measured on days 8 and 15 after eltrombopag treatment increase to \> 50,000/uL counts on other days are just used to be sure the ones on days 8 and 15 are reasonably accurate and representative
COMPLETED
PHASE2
20 participants
platelet counts on days 8 and 15
2019-03-18
Participant Flow
patients with persistent or chronic ITP willing to undergo washout period and then multiple visits (7) in 2 weeks period including 3 larger blood draws
Participant milestones
| Measure |
Eltrombopag
Promacta (eltrombopag): Subjects will be treated with eltrombopag 75 mg once daily. Patients will be monitored 3 times a week for the first 2 weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for 3-4 months.
first blood draw before taking eltrombopag
|
Eltombopag Then Romiplostim
patients who receive eltrombopag and then are treated with romiplostim (nplate) to ascertain parallelism between the two agents
|
Healthy Volunteer
one blood draw only
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
3
|
10
|
|
Overall Study
COMPLETED
|
7
|
3
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Eltrombopag and the Bcl-extra-large (xL) Pathway in Idiopathic Thrombocytopenic Purpura (ITP)
Baseline characteristics by cohort
| Measure |
Eltrombopag Arm
n=7 Participants
Participants will be treated with eltrombopag 75 mg once daily. Participants will be monitored three times a week for the first two weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for four months.
|
Eltrombopag Receiving Romiplostim
n=3 Participants
Three Participants who had been on eltrombopag in the past will undergo a washout period and will be treated with Romiplostim 10 ug/kg/weekly for 2 weeks. Participants on Romiplostim will be monitored three times a week for two weeks.
|
Healthy Volunteers
n=10 Participants
single blood draw in healthy volunteers (controls)
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
3 participants
n=7 Participants
|
10 participants
n=5 Participants
|
20 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: platelet counts on days 8 and 15Population: 0 participants were analyzed in the healthy control arm because healthy controls did not have any blood draws on day 8 and 15 or receive the intervention and hence data was not collected for these participants
number of patients in whom Platelet Counts measured on days 8 and 15 after eltrombopag treatment increase to \> 50,000/uL counts on other days are just used to be sure the ones on days 8 and 15 are reasonably accurate and representative
Outcome measures
| Measure |
Eltrombopag Arm
n=7 Participants
Participants will be treated with eltrombopag 75 mg once daily. Participants will be monitored three times a week for the first two weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for four months.
|
Eltrombopag Then Romiplostim
n=3 Participants
Three Participants from Eltrombopag arm will undergo second washout period and will be treated with Romiplostim 10 ug/kg/weekly for 2 weeks. Participants on Romiplostim will be monitored three times a week for two weeks exactly like when they received Eltrombopag.
|
Healthy Controls
10 normal volunteers for a single blood draw
|
|---|---|---|---|
|
Number of Patients for Whom Eltrombopag Increases the Platelet Count to > 50,000/uL
pts with platelet counts > 50,000/uL on day 8
|
6 participants
|
3 participants
|
—
|
|
Number of Patients for Whom Eltrombopag Increases the Platelet Count to > 50,000/uL
Pts with platelet counts > 50,000/uL on day 15
|
6 participants
|
3 participants
|
—
|
PRIMARY outcome
Timeframe: platelet counts on days 8 and 15number of participants in whom platelet counts measured on day 8 and day 15 after treatment(s) with romiplostim 10 micrograms/kg on days 1 and 8
Outcome measures
| Measure |
Eltrombopag Arm
n=3 Participants
Participants will be treated with eltrombopag 75 mg once daily. Participants will be monitored three times a week for the first two weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for four months.
|
Eltrombopag Then Romiplostim
Three Participants from Eltrombopag arm will undergo second washout period and will be treated with Romiplostim 10 ug/kg/weekly for 2 weeks. Participants on Romiplostim will be monitored three times a week for two weeks exactly like when they received Eltrombopag.
|
Healthy Controls
10 normal volunteers for a single blood draw
|
|---|---|---|---|
|
Number of Patients Who Received Romiplostim and Increased Their Platelet Counts to > 50,000/uL
plt cts > 50,000/uL on day 8
|
3 participants
|
—
|
—
|
|
Number of Patients Who Received Romiplostim and Increased Their Platelet Counts to > 50,000/uL
plt cts > 50,000/uL on day 15
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: on days 8 and 15Population: 0 participants were analyzed in the healthy controls arm because healthy controls did not have any blood draw on day 8 and 15 or receive the intervention and hence data was not collected for these participants
To assess the safety of eltrombopag, in particular the number of patients with serious adverse events and/or abnormal liver tests reaching a level of more than twice the upper limit of normal for the test these outcomes were assessed periodically for liver tests but other SAEs were not systematically assessed but only with complaints or events
Outcome measures
| Measure |
Eltrombopag Arm
n=10 Participants
Participants will be treated with eltrombopag 75 mg once daily. Participants will be monitored three times a week for the first two weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for four months.
|
Eltrombopag Then Romiplostim
n=3 Participants
Three Participants from Eltrombopag arm will undergo second washout period and will be treated with Romiplostim 10 ug/kg/weekly for 2 weeks. Participants on Romiplostim will be monitored three times a week for two weeks exactly like when they received Eltrombopag.
|
Healthy Controls
10 normal volunteers for a single blood draw
|
|---|---|---|---|
|
How Many Patients Developed SAEs and/or Abnormal Liver Tests to a Level > 2 Times the Upper Limit of Normal
number of patients with Abnl LFTs on day 8
|
1 participants
|
0 participants
|
—
|
|
How Many Patients Developed SAEs and/or Abnormal Liver Tests to a Level > 2 Times the Upper Limit of Normal
number of patients Abnl LFTs on day 15
|
1 participants
|
0 participants
|
—
|
|
How Many Patients Developed SAEs and/or Abnormal Liver Tests to a Level > 2 Times the Upper Limit of Normal
number of patients with an SAE on day 8
|
0 participants
|
0 participants
|
—
|
|
How Many Patients Developed SAEs and/or Abnormal Liver Tests to a Level > 2 Times the Upper Limit of Normal
number of patients with an SAE on day 15
|
0 participants
|
0 participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: testing on days 8 and 15Population: 0 participants were analyzed in the healthy controls arm because healthy controls did not have any blood draw on day 8 and 15 or receive the intervention and hence data was not collected for these participants
Samples were drawn weekly for 2 weeks on days 1, 8, and 15 for the treatment arms and day 1 for the healthy control group. Platelet samples were exposed to small molecule Bcl-xL inhibitor, ABT-737 ex-vivo to explore resistance to apoptosis by determining the half maximal inhibitory concentration (IC50) which was measured for each weekly sample drawn. If the half maximal concentration of ABT737 was increased this meant increased resistance to apoptosis. The AKT pathway intermediates were measured since these would indicate the mechanism of the platelet resistance to apoptosis so the two sets of measures confirm each other the AIPF is a measure of how many new platelets are made and the large platelets are similar to that
Outcome measures
| Measure |
Eltrombopag Arm
n=7 Participants
Participants will be treated with eltrombopag 75 mg once daily. Participants will be monitored three times a week for the first two weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for four months.
|
Eltrombopag Then Romiplostim
n=3 Participants
Three Participants from Eltrombopag arm will undergo second washout period and will be treated with Romiplostim 10 ug/kg/weekly for 2 weeks. Participants on Romiplostim will be monitored three times a week for two weeks exactly like when they received Eltrombopag.
|
Healthy Controls
10 normal volunteers for a single blood draw
|
|---|---|---|---|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
platelet apoptosis increase on day 8
|
7 Participants
|
3 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
platelet apoptosis increase on day 15
|
2 Participants
|
0 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
increase in intracellular AKT intermediates day 8
|
7 Participants
|
3 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
increase in intracellular AKT intermediates day 15
|
0 Participants
|
1 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
increase in A-IPF day 8
|
7 Participants
|
3 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
increase in A-IPF day 15
|
7 Participants
|
3 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
increase in large platelets day 8
|
7 Participants
|
3 Participants
|
—
|
|
Change From Baseline After Eltrombopag Treatment of Platelet Parameters
increase in large platelets day 15
|
7 Participants
|
3 Participants
|
—
|
Adverse Events
Eltrombopag
Romiplostim
Healthy Volunteers
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Eltrombopag
n=10 participants at risk
Ten participants will be treated with eltrombopag 75 mg once daily. Participants will be monitored three times a week for the first two weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for four months.
|
Romiplostim
n=3 participants at risk
Three Participants who had been on eltrombopag will undergo a washout period and will be treated with Romiplostim 10 ug/kg/weekly for 2 weeks. Participants on Romiplostim will be monitored three times a week for two weeks.
|
Healthy Volunteers
n=10 participants at risk
single blood draw in healthy controls/volunteers
|
|---|---|---|---|
|
Hepatobiliary disorders
increase in LFTs
|
10.0%
1/10 • Number of events 1 • data for investigation collected over 2 weeks in all patients: 7 with eltrombopag alone and 3 with eltrombopag first and, then after a washout period, romiplostim later this would be 10 for eltrombopag and 3 for romiplostim additional medication provided as incentive to patients to enter the study there was a single blood draw without incident in the 10 healthy volunteers
patients were asked for concomitant meds and Adverse Events on every visit
|
0.00%
0/3 • data for investigation collected over 2 weeks in all patients: 7 with eltrombopag alone and 3 with eltrombopag first and, then after a washout period, romiplostim later this would be 10 for eltrombopag and 3 for romiplostim additional medication provided as incentive to patients to enter the study there was a single blood draw without incident in the 10 healthy volunteers
patients were asked for concomitant meds and Adverse Events on every visit
|
0.00%
0/10 • data for investigation collected over 2 weeks in all patients: 7 with eltrombopag alone and 3 with eltrombopag first and, then after a washout period, romiplostim later this would be 10 for eltrombopag and 3 for romiplostim additional medication provided as incentive to patients to enter the study there was a single blood draw without incident in the 10 healthy volunteers
patients were asked for concomitant meds and Adverse Events on every visit
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place