A Phase 3, Multicenter, Randomized, Double-blind, Active-controlled, Parallel-group Trial With an Open-label Extension Phase to Evaluate the Efficacy and Safety of Oral E5501 Versus Eltrombopag, in Adults With Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenic Purpura)

Inclusion:

• Men and women greater than or equal to 18 years of age
• Subjects diagnosed with cITP (greater than or equal to 12 months duration) according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines, and an average of 2 platelet counts less than 30x109/L). The physical exam should not suggest any disease which may cause thrombocytopenia other than ITP.
• Subjects who previously received one or more ITP therapies(including, but not limited to corticosteroids, immunoglobulins, azathioprine, dnazol, cyclophosphamide and/or rituximab).
• Subjects must have had either initially responded (platelet count greater than 50x109/L) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndrome (MDS) or other causes of thrombocytopenia.
• Prothrombin time/International Normalized Ratio (PT/INR) and activated partial thromboplastin time (aPTT) must have been within 80% to 120% of the normal range with no history of hypercoagulable state.
• A complete blood count within the reference range (including white blood count [WBC] differential not indicative of a disorder other than ITP), with the following exceptions: hemoglobin:subjects with hemoglobin levels between 10g/dL (100g/L) and the lower limit of normal (LLN) are eligible for inclusion, if anemia was clearly attributable to ITP (excessive blood loss); Absolute neutrophil count (ANC) greater than or equal to 1500/uL (1.5x109/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable)

Exclusion:

Core Study

1. Subjects with known secondary immune thrombocytopenia (e.g., subjects with known Helicobacter pylori-induced ITP, infected with known human immunodeficiency virus [HIV] or hepatitis C virus [HCV] or with known systemic lupus erythematosus [SLE])
2. Subjects considered unable, or unwilling to comply with the study protocol requirements or give informed consent, as determined by the investigator
3. Subjects with significant medical conditions that may impact the safety of the subject or interpretation of the study results (e.g., acute hepatitis, active chronic hepatitis; lymphoproliferative disease; myeloproliferative disorders, leukemia)
4. History of MDS
5. History of pernicious anemia or subjects with vitamin B12 deficiency who have not had pernicious anemia excluded as a cause
6. Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, or pulmonary embolism), and more than two of the following risk factors: estrogen-containing hormone replacement or contraceptive therapies, 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
7. Subjects with a history of significant cardiovascular disease (e.g., congestive heart failure [CHF] New York Heart Association Grade III/IV), arrhythmia known to increase the risk of thromboembolic events [e.g., atrial fibrillation], subjects with a QT interval corrected for heart rate of > 450 msec, angina, unstable angina, coronary artery stent placement, angioplasty, or coronary artery bypass grafting)
8. Subjects with a history of cirrhosis, portal hypertension, and chronic active hepatitis
9. Subjects with concurrent malignant disease
10. Use of immunoglobulins (IVIg and anti-D) within 1 week of randomization
11. Splenectomy or use of rituximab within 12 weeks of randomization
12. Use of romiplostim or eltrombopag within 4 weeks of randomization
13. Subjects who are currently treated with corticosteroids or azathioprine but have not been receiving a stable dose for at least 4 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
14. Subjects who are currently treated with MMF, CsA, or danazol but have not been receiving a stable dose for at least 12 weeks prior to randomization or have not completed these therapies more than 4 weeks prior to randomization
15. Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of randomization.
16. Subjects who are currently treated with PPIs or H2 antagonist therapy but have not been receiving a stable dose for at least 6 weeks prior to randomization or have not completed these therapies more than 2 weeks prior to randomization
17. Fasting gastrin-17 blood levels exceeding ULN (including subjects on PPIs and H2 antagonists) at Screening
18. Blood creatinine exceeding ULN by more than 20% OR total albumin below the LLN by 10% (revised per Amendment 01)
19. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels exceeding 2 times the ULN; total bilirubin exceeding 1.5 times the ULN
20. Subjects with a history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy. Subjects with a history of ITP treatment with cytotoxic chemotherapy are still eligible for enrollment.
21. Females who are pregnant (positive beta-human chorionic gonadotropin [β-hCG] test) or breastfeeding
22. Subjects with a known allergy to E5501 or eltrombopag and any of their excipients
23. Subjects with a history of significant aminotransferase elevations while receiving eltrombopag (defined as ALT and/or AST elevation >3 x ULN)
24. Subjects who are known nonresponders (defined as platelet counts that never exceed 50 x 109/L) to all previous TPO agonist therapy (including previous E5501 therapy) who do not have a bone marrow examination consistent with ITP taken at any point after failure of TPO therapy to rule out MDS or other causes of thrombocytopenia