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)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01433978
First received: September 13, 2011
Last updated: June 26, 2014
Last verified: October 2013
  Purpose

Approximately 286 subjects 18 years of age and over who meet all the eligibility requirements will be randomized. Splenectomized subjects must make up at least 35% of the study population. No single platelet count should be greater than 35x109/L. Subjects will be centrally stratified at randomization by splenectomy status, baseline platelet count, and use of concomitant ITP medication at baseline and will be randomized to receive either double-blind E5501 or eltrombopag in a 1:1 ratio. Subjects will receive blinded therapy at a starting dose of 20mg E5501 once daily or 50mg eltrombopag once daily. Subjects will be allowed to have their dose titrated up (maximum dose 40mg E5501 and 75mg for eltrombopag) or down (minimum dose 5mg for E5501 and 25mg for eltrombopag)depending on their response to study drug. The goal of dose modification is to maintain the platelet count at levels greater than or equal to 50x109/L and less than or equal to 150x109/L, and to decrease the need for ITP-directed concomitant medications. The study will consist of three phases: prerandomization, Randomization (Core Study) and the extension study. The duration of treatment in the Core study is 26 weeks and the extension study is up to 2 years.


Condition Intervention Phase
Idiopathic Thrombocytopenic Purpura
Drug: Eltrombopag
Drug: E5501 - Avatrombopag maleate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Durable platelet response as defined by the proportion of subjects who have at least 6 of 8 weekly platelet responses during the last 8 weeks of treatment over the 6-month treatment period in absence of rescue therapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2012
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E5501 - Avatrombopag maleate Drug: E5501 - Avatrombopag maleate
administered orally as 5mg, 10mg, 20mg, or 40mg in a flexible dose design
Active Comparator: Eltrombopag Drug: Eltrombopag
administered orally as 25mg, 50mg, or 75mg in a flexible dose design

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01433978

Locations
United States, South Dakota
Prairie Lakes Health Care System
Watertown, South Dakota, United States
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Joe McIntosh Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01433978     History of Changes
Other Study ID Numbers: E5501-G000-305, 2011-000831-10
Study First Received: September 13, 2011
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thrombocytopenia
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Autoimmune Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Hemorrhage
Hemorrhagic Disorders
Immune System Diseases
Pathologic Processes
Signs and Symptoms
Skin Manifestations
Thrombotic Microangiopathies

ClinicalTrials.gov processed this record on October 20, 2014