Repeated Exposure to Eltrombopag in Adults With Idiopathic Thrombocytopenic Purpura (REPEAT)

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:
• 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.
• 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 p