A Longitudinal 2-year Bone Marrow Study of Eltrombopag in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

Inclusion Criteria:

• Subjects must have signed and dated a written informed consent and be able tounderstand and comply with protocol requirements and instructions.

• Adults (≥18 years) diagnosed with chronic ITP according to the American Society forHematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003; Provan, 2009]. In addition, a peripheral blood smear shouldsupport the diagnosis of ITP with no evidence of other disease causative ofthrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physicalexamination should not suggest any disease, which may cause thrombocytopenia otherthan ITP.

• Subjects must be physically eligible for serial bone marrow biopsies and must have abone marrow biopsy performed during screening, and be willing to remain on the studyfor at least 2 years with annual bone marrow biopsies.

• Subjects, who previously received eltrombopag or romiplostim, must have completedtreatment with these therapies at least 6 months prior to the screening bone marrowbiopsy.

• Subjects must have the following clinical chemistry values:

• ALT and AST < 2xULN;

• Bilirubin <1.5xULN (except for Gilbert's Syndrome);

• Subjects are practicing an acceptable method of contraception as specified in theprotocol.

• In France, subjects will be eligible for inclusion in this study, only if eitheraffiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• Subjects with any clinically relevant abnormality, other than ITP, or any othermedical condition or circumstance, which in the opinion of the investigator makes thesubject unsuitable for participation in the study or suggests another primarydiagnosis (e.g., thrombocytopenia is secondary to another disease).

• Subjects with any concurrent malignant disease and/or a recent history of cancertreatment with systemic chemotherapy and/or radiotherapy. Exception: Subjects with a history of completely resected non-melanoma skin cancer orsuccessfully treated in situ carcinoma are eligible.

• Subjects with any prior history of arterial or venous thrombosis (stroke, transientischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism),AND ≥ two of the following risk factors: hormone replacement therapy, systemiccontraception (containing estrogen), smoking, diabetes, hypercholesterolemia,hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIIIdeficiency, etc), or any family history of arterial or venous thrombosis.

• Subjects with screening bone marrow fibers of either MF Grade 3 using EuropeanConsensus scale or Grade 4 using Bauermeister scale.

• Subjects with a QTc >450 msec or > 480 msec for subjects with Bundle Branch Block.

• Female subjects who are nursing or pregnant (positive serum or urine β-human chorionicgonadotrophin (β-hCG) pregnancy test) at screening.

• Subjects treated with an investigational drug (other than a thrombopopoetin-receptor (TPO-R) agonist) within 30 days or five half-lives (whichever is longer) preceding thefirst dose of eltrombopag in the study. (For romiplostim or eltrombopag, see inclusioncriterion #4).

• Subjects treated with any TPO-R agonist other than romiplostim or eltrombopag.

• Subjects with recent history of alcohol/drug abuse as determined by the investigator.