Repeated Exposure to Eltrombopag in Adults With Idiopathic Thrombocytopenic Purpura (REPEAT)
Condition: Purpura, Thrombocytopaenic, Idiopathic
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
Intervention: eltrombopag
Intervention description: experimental
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: idiopathic thrombocytopenic purpura; ITP; thrombocytopenia; platelets

Summary:

      This open-label, repeat dosing study, TRA108057, will evaluate the efficacy, safety and
      tolerability of eltrombopag, when administered in a repeat, cyclic dosing schedule. The study
      will describe the effect of repeated (3 cycles), intermittent dosing of eltrombopag on the
      pharmacodynamics and durability of eltrombopag response as measured by the peripheral
      platelet counts.

      For more information or to see if you qualify, please visit: http://www.itpstudy.com/gov
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects eligible for enrolment in the study must meet all of the following criteria:

          -  Subject has signed and dated a written inform consent.

          -  Adults (≥18 years) diagnosed with chronic ITP according to the American Society of
             Hematology/British Committee for Standards in Hematology guidelines, and a platelet
             count between ≥20 Gi/L and ≤50 Gi/L on Day 1 (or within 24 hours prior to dosing on
             Day 1). In addition, a peripheral blood smear should support the diagnosis of ITP with
             no evidence of other causes of thrombocytopenia (e.g. pseudothrombocytopenia,
             myelodysplasia). The physical examination should not suggest any disease which may
             cause thrombocytopenia other than ITP.

          -  Subjects who have previously received one or more prior ITP therapies. Previous
             treatments for ITP include but are not limited to corticosteroids, immunoglobulins,
             azathioprine, danazol, cyclophosphamide and/or rituximab.

          -  Subjects must have either initially responded (platelet count >100 Gi/L) to a previous
             ITP therapy or have had a bone marrow biopsy consistent with ITP within 3 years to
             rule out myelodysplastic syndromes or other causes of thrombocytopenia.

          -  It is important to clearly differentiate the effect of eltrombopag on platelet count
             from the treatment effects of prior and concomitant ITP therapies. Therefore:

               1. Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been
                  completed at least 1 week prior to randomization and the platelet count must show
                  a clear downward trend after the last treatment with immunoglobulins. Previous
                  treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been
                  completed at least 4 weeks prior to randomization, or clearly be ineffective.

               2. Subjects treated with concomitant ITP medication (e.g. corticosteroids or
                  azathioprine) must be receiving a dose that has been stable for a least 4 weeks
                  prior to randomization. Subjects treated with cyclosporine A, mycophenolate
                  mofetil or danazol must be receiving a dose that has been stable for at least 3
                  months prior to randomization.

          -  Prothrombin time and activated partial thromboplastin time must be within 80 to 120%
             of normal range with no history of hypercoagulable state.

          -  A complete blood count (CBC), within the reference range (including differential not
             indicative of a disorder other than ITP), with the following exceptions:

          -  Platelet count between ≥20 Gi/L and ≤50 Gi/L on Day 1 (or within 24 hours of Day 1) is
             required for inclusion.

          -  Hemoglobin: Subjects with hemoglobin levels between 10g/dL (100g/L) and the lower
             limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP
             (excessive blood loss).

          -  Absolute Neutrophil Count (ANC ) >1500/mL (1.5 x 10^9/L) is required for inclusion
             (elevated White Blood Cells/ANC above the reference range due to steroid treatment is
             acceptable).

          -  The following clinical chemistries MUST NOT exceed the normal reference range by more
             than 20%: creatinine, Alanine aminotransferase, Aspartate aminotransferase, total
             bilirubin, total albumin and alkaline phosphatase.

          -  Subject is practicing an acceptable method of contraception (documented in chart).
             Female subjects (or female partners of male subjects) must either be of
             non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal
             ligation or post-menopausal >1 year), or of childbearing potential and use of one of
             the following acceptable methods of contraception from two weeks prior to
             administration of study medication, throughout the study, and 28 days after completion
             or premature discontinuation from the study:

        Complete abstinence from intercourse; Intrauterine device (IUD); Two forms of barrier
        contraception (diaphragm plus spermicide, and for males condom plus spermicide); Male
        partner is sterile prior to entry into the study and is the only partner of the female;
        Systemic contraceptives (combined or progesterone only).

          -  Subject is able to understand and comply with protocol requirements and instructions
             and intends to complete the study as planned.

        Exclusion Criteria:

        A subject will NOT be eligible for inclusion in this study if any of the following criteria
        apply:

          -  Any clinically relevant abnormality, other than ITP, identified on the screening
             examination or any other medical condition or circumstance, which in the opinion of
             the investigator makes the subject unsuitable for participation in the study or
             suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another
             disease).

          -  Concurrent malignant disease and/or history of cancer treatment with cytotoxic
             chemotherapy and/or radiotherapy.

          -  Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack,
             myocardial infarction, deep vein thrombosis or pulmonary embolism), AND ≥ two of the
             following risk factors: hormone replacement therapy, systemic contraception
             (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for
             hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden,
             Antithrombin III deficiency, etc), or any other family history of arterial or venous
             thrombosis.

          -  Pre-existing cardiovascular disease (congestive heart failure, New York Heart
             Association Grade III/IV), or arrhythmia known to increase the risk of thromboembolic
             events (e.g. atrial fibrillation), or subjects with a QTc >450 msec.

          -  Female subjects who are nursing or pregnant (positive serum or urine b-human chorionic
             gonadotrophin pregnancy test) at screening or pre-dose on Day 1.

          -  History of alcohol/drug abuse.

          -  Treatment with an investigational drug within 30 days or five half-lives (whichever is
             longer) preceding the first dose of study medication.

          -  Subject treated with drugs that affect platelet function (including but not limited to
             aspirin, clopidogrel and/or Non Steroidal Anti Inflammatory Drugs) or anti-coagulants
             for > 3 consecutive days within 2 weeks of the study start and until the end of the
             study.

          -  History of platelet agglutination abnormality that prevents reliable measurement of
             platelet counts.

          -  All subjects with secondary immune thrombocytopenia, including those with laboratory
             or clinical evidence of human immunodeficiency virus (HIV) infection,
             anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus
             infection, or any evidence for active hepatitis at the time of subject screening. If a
             potential subject has no clinical history that would support HIV infection or
             hepatitis infection, no further laboratory screening is necessary; however, standard
             medical practice would suggest further evaluation of patients who have risk factors
             for these infections.

          -  Previous participation in a clinical study with eltrombopag.

          -  Subjects planning to have cataract surgery.

          -  In France, a subject is neither affiliated with nor a beneficiary of a social security
             category.