Safety and Efficacy of Eltrombopag at Escalated Doses
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01880047|
Recruitment Status : Completed
First Posted : June 18, 2013
Results First Posted : June 11, 2019
Last Update Posted : June 11, 2019
Study rationale is based on the data that in previous clinical studies of eltrombopag in ITP there are some patients who have been reported as non responders at the maximal approved dose of 75 mg daily. The trend in both normal volunteers and in patients with ITP suggest and increasing response rate with increased doses of eltrombopag up to a dose of 75mg. Previously published data has shown no overt increase in toxicity in normal volunteers, oncology patients and aplastic anemia patients treated with escalated doses as high or higher than those proposed in this study.
It therefore seems possible that in ITP patients who did not respond to a dose of 75mg daily, eltrombopag could be more effective at a higher dose. We propose a double blind randomized controlled trial in ITP patients who have been defined as non-responders at the maximum dose (75mg) of eltrombopag, assessing efficacy and toxicity at higher daily doses (100mg, 125 mg, 150 mg)
|Condition or disease||Intervention/treatment||Phase|
|Immune Thrombocytopenia Platelet Disorder||Drug: Eltrombopag Drug: Placebo||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Safety and Efficacy of Eltrombopag at Escalated Doses up to 150mg in Patients With Persistent and Chronic Immune Thrombocytopenia (ITP) Not Responsive to 75 mg|
|Actual Study Start Date :||February 2013|
|Actual Primary Completion Date :||February 15, 2017|
|Actual Study Completion Date :||October 16, 2017|
Active Comparator: Eltrombopag
Subjects in the study will receive 75 mg eltrombopag and then be randomized to receive either an additional 25 mg of eltrombopag or matching placebo tablet dispensed by the research pharmacy. Subjects and investigators will be blinded to randomization. Randomization will be stratified according to splenectomy status. Randomization will be performed at the time of informed consent with a computer generated randomization table. Subjects and investigators will be blinded to assignment and treatment in this phase.
Eltrombopag will be administered for 8 weeks or until the platelet count exceeds 150,000; at this point dosing will stop, subject will be considered a responder and the subject will eligible for entering Part 2 (the long term treatment part of the study. The dose at which the subject achieved the primary endpoint (> 50,000 and increase by > 20,000) will be considered the dose of response. Dose escalation will continue, despite satisfaction of the primary endpoint of study (> 50,000 and > 20,000 above baseline), unless the platelet count reaches the lower limit of normal range 150,000. Subjects will stop study medication if the platelet count is within the normal range, thereby minimizing any safety risk associated with elevated platelet count.
Placebo Comparator: Placebo
Subjects will be randomly allocated in a two to one ratio to receive treatment or placebo. All subjects in the study will receive 75 mg eltrombopag and then be randomized to receive either an additional 25 mg of eltrombopag or matching placebo tablet dispensed by the research pharmacy. Subjects and investigators will be blinded to randomization. Randomization will be stratified according to splenectomy status.
- Number of Patients Responding to >75mg Daily as Defined by a Rise in Platelet Count by 20,000/Microliter, With a Total Platelet Count >50,000/Microliter, ON TWO CONSECUTIVE OCCASIONS During the 8 Week Period [ Time Frame: 8 weeks ]To determine if patients with chronic ITP who do not respond to 75 mg of eltrombopag daily given for at least 3 weeks but then do respond to eltrombopag given daily first for 2 weeks at doses of 100, then for 2 weeks at 125 mg and finally for 4 weeks at a dose of 150mg daily. Response will be defined as 2 consecutive platelet counts of > 50,000 with an increase of > 20,000 from the study baseline within the 8 week increased dose window not as a result of rescue treatment.
- Number of Particiapants With Drug Related Adverse Events [ Time Frame: 8 weeks ]Monitoring for AEs, SAEs, abnormalities in liver or kidney function, thrombotic complications, hematologic malignancies, parameters suggesting bone marrow fibrosis (a bone marrow may be done at the discretion of the investigator), cataracts.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01880047
|United States, New York|
|Weill Cornell Medicine|
|New York, New York, United States, 10065|
|Principal Investigator:||Sujit Sheth, M.D.||Weill Cornell Medicine|