A Phase 3, Multicenter, Randomized, Double-blind,Active-controlled, Parallel-group Trial With an Open-labelExtension Phase to Evaluate the Efficacy and Safety of OralE5501 Versus Eltrombopag, in Adults With Chronic ImmuneThrombocytopenia (Idiopathic

• Status: Terminated
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Core study:

To compare the efficacy of avatrombopag (in addition to standard) of care to eltrombopag (in addition to standard of care) for the treatment of adult participants with chronic immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) as measured by durable platelet response.

Open-label Extension Phase:

To evaluate the safety and tolerability of long-term therapy with avatrombopag in participants with chronic ITP (cITP).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eisai Inc.
• Treatments: Maleic acid

Criteria

Inclusion Criteria:

1. Men and women greater than or equal to 18 years of age.

2. Participants 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 30x10^9/L). The physical exam should not suggest any disease which may cause thrombocytopenia other than ITP.

3. Participants who previously received one or more ITP therapies (including, but not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab).

4. Participants must have had either initially responded (platelet count greater than 50x10^9/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.

5. 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.

6. 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: a) Hemoglobin: participants with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal (LLN) are eligible for inclusion, if anemia was clearly attributable to ITP (excessive blood loss); b) Absolute neutrophil count (ANC) greater than or equal to 1500/uL (1.5x10^9/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable).

Exclusion Criteria:

Core Study

1. Participants with known secondary immune thrombocytopenia (e.g., participants 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. Participants considered unable, or unwilling to comply with the study protocol requirements or give informed consent, as determined by the investigator.

3. Participants with significant medical conditions that may impact the safety of the participant 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 participants 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. Participants 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], participants 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. Participants with a history of cirrhosis, portal hypertension, and chronic active hepatitis.

9. Participants 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. Participants 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. Participants 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. Participants 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. Participants with a history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.

21. Participants with a history of ITP treatment with cytotoxic chemotherapy are still eligible for enrollment.

22. Females who are pregnant (positive beta-human chorionic gonadotropin [B-hCG] test) or breastfeeding.

23. Participants with a known allergy to E5501 or eltrombopag and any of their excipients.

24. Participants with a history of significant aminotransferase elevations while receiving eltrombopag (defined as ALT and/or AST elevation >3 x ULN).

25. Participants who are known nonresponders (defined as platelet counts that never exceed 50 x 10^9/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.