Safety and Efficacy of Eltrombopag at Escalated Doses
Condition: Immune Thrombocytopenia; Platelet Disorder
MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders
Intervention: Eltrombopag; Placebo
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 35.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Immune Thrombocytopenia; ITP; Eltrombopag; Promacta

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)
    

Eligibility 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