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Safety and Efficacy of Eltrombopag at Escalated Doses

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ClinicalTrials.gov Identifier: NCT01880047
Recruitment Status : Completed
First Posted : June 18, 2013
Results First Posted : June 11, 2019
Last Update Posted : June 11, 2019
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: Eltrombopag
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.
Other Names:
  • SB-497115-GR
  • Promacta

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.
Drug: Placebo



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject or their parent/ guardian has signed and dated a written informed consent
  • Male and Females aged 12 years or older diagnosed with chronic ITP according to the new consensus guidelines
  • No indication of a disease which may cause thrombocytopenia other than ITP----no specific testing required
  • Subjects with thrombocytopenia ≤ 50,000 /uL after at least 21 days of daily dosage with eltrombopag 75mg
  • Stable dosage of concomitant treatments for ITP

    ≥ 2 weeks or longer (corticosteroids);

  • At least 2 weeks from rescue therapy for ITP (WinRho, Intravenous Immunoglobulin (IVIG), corticosteroids, platelet transfusion)
  • At least 4 weeks from rituximab treatment
  • Pregnant or Lactating Women are excluded
  • Women of child-bearing age with a negative pregnancy test within 7 days of enrollment and who agree to use acceptable methods of birth control will be eligible for this study
  • Female subjects or female partners of male subjects must either be of non-child bearing potential (hysterectomy, bilateral ovariectomy, bilateral tubal ligation or post menopausal for more than one year) OR, if of child bearing potential, using one of the following highly effective methods of contraception.
  • complete abstinence from intercourse
  • Intrauterine device (IUD)
  • Two forms of barrier contraception. diaphragm plus spermicide, or for males condoms plus spermicide.
  • Male partner is sterile and is the only partner of the female.
  • Systemic contraceptives (combined oral progesterone only)

Exclusion Criteria:

  • Previous history of eltrombopag-related liver function test (LFT) elevation that required interruption of treatment
  • Previous history of immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag
  • HIV Infection
  • History of Arterial of Venous Thrombosis within the past year or requiring ongoing therapy
  • Active Hepatitis C infection
  • Treatment with medications that affect platelet function ( including but not limited to Aspirin, Clopidogrel and /or NSAIDs) or anti-coagulant medications
  • Elevated Aspartate Aminotransferase(AST/ALT) or Creatinine > 1.5 times upper limit of normal in 4 weeks prior to enrollment*
  • Abnormalities in white blood cell count (WBC), automatic neutrophil count (ANC), and Hemoglobin > 1.5 times upper or lower limit of normal*
  • * Subjects can be rescreened to be included

Information from the National Library of Medicine

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


Locations
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United States, New York
Weill Cornell Medicine
New York, New York, United States, 10065
Sponsors and Collaborators
Weill Medical College of Cornell University
Novartis
Investigators
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Principal Investigator: Sujit Sheth, M.D. Weill Cornell Medicine
  Study Documents (Full-Text)

Documents provided by Weill Medical College of Cornell University:

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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01880047     History of Changes
Other Study ID Numbers: 116862
First Posted: June 18, 2013    Key Record Dates
Results First Posted: June 11, 2019
Last Update Posted: June 11, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Weill Medical College of Cornell University:
Immune Thrombocytopenia
ITP
Eltrombopag
Promacta
Additional relevant MeSH terms:
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Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms