Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01438840
First received: September 19, 2011
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

Approximately 45 subjects 18 years of age and over who meet all the eligibility requirements will be randomized. No single platelet count should be greater than 35x10^9/L (liter). Subjects will be centrally stratified at randomization baseline platelet count, and use of concomitant Idiopathic Thrombocytopenia Purpura (ITP) medication at baseline and will be randomized to receive either double-blind E5501 or placebo in a 2:1 ratio. Subjects will receive blinded therapy at a starting dose of 20mg E5501 or placebo once daily. Subjects will be allowed to have their dose titrated up (maximum dose 40mg E5501 or matching placebo) or down (minimum dose 5mg for E5501 or matching placebo) 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 50x10^9/L and less than or equal to 150x10^9/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
Chronic Thrombocytopenia
Immune Thrombocytopenia
Drug: E5501 - Avatrombopag maleate
Drug: E5501 - Avatrombopag maleate Matching Placebo
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, Placebo-controlled, Parallel-group Trial With an Open-label Extension Phase to Evaluate the Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Idiopathic Thrombocytopenia Purpura)

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Cumulative Number Of Weeks Of Platelet Response Over 6 Months of Treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of Participants with a Platelet Response At Day 8 [ Time Frame: 8 days ] [ Designated as safety issue: No ]
    Platelet response rate at Day 8 defined by the proportion of participants with a platelet response >= 50 X 10^9/L (liter) at Day 8. Subjects with missing platelet counts at Day 8 or use of a rescue therapy before or on Day 8 will be considered platelet nonresponders.


Enrollment: 49
Study Start Date: March 2012
Study Completion Date: March 2014
Primary Completion Date: November 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, 30mg or 40mg in a flexidose design. Starting dose of 20 mg, with dose titration down to 5 mg or up to 40 mg as per specified guidelines.
Placebo Comparator: E5501 - Avatrombopag maleate Matching Placebo Drug: E5501 - Avatrombopag maleate Matching Placebo
Matching Placebo administered orally as 5mg, 10mg, 20mg, 30mg or 40mg in a flexidose design. Starting dose of 20 mg, with dose titration down to 5 mg or up to 40 mg as per specified guidelines.

  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 (Chronic Idiopathic Thrombocytopenia Purpura) (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 greater than 30x10^9/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, danazol, cyclophosphamide and/or rituximab).
  • Subjects 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.
  • 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 (grams/ deciliter) (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 (1.5x10^9/L) (elevated WBC/ANC due to corticosteroid treatment is acceptable)

Exclusion:

  1. Subjects with known secondary immune thrombocytopenia (e.g., with known Helicobacter pylori-induced ITP subjects infected with known human immunodeficiency virus [HIV] or hepatitis C virus [HCV] or subjects with known systemic lupus erythematosus). (Revised per Amendment 01)
  2. Subjects with significant medical conditions that may impact on the safety of the subject or interpretation of the study results (e.g., acute hepatitis, active chronic hepatitis; lymphoproliferative disease; myeloproliferative disorders, leukemia).
  3. History of MDS (Myelodysplastic Syndrome)
  4. History of gastric atrophy (added per Amendment 01)
  5. History of pernicious anemia or subjects with vitamin B12 deficiency (defined as <LLN) who have not had pernicious anemia excluded as a cause (added per Amendment 01)
  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: hormone replacement therapy, 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, coronary artery stent placement, angioplasty, 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 the ULN at Screening for subjects not on PPIs or H2 antagonists (Revised per Amendment 01)
  18. Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) at Screening for subjects on PPIs or H2 antagonists (Added per Amendment 01)
  19. Blood creatinine exceeding ULN by more than 20% OR total albumin below the lower limit of normal (LLN) by 10%
  20. Alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) levels exceeding 3 times the ULN ORtotal bilirubin exceeding 2 times the ULN
  21. 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.
  22. Females who are pregnant (positive beta-human chorionic gonadotropin positive [β-hCG] test) or breastfeeding
  23. Subjects with a known allergy to E5501 or its excipients
  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: NCT01438840

Locations
Australia
Adelaide, Australia
Canberra, Australia
Belgium
Brugge, Belgium
Bulgaria
Plovdiv, Bulgaria
Sofia, Bulgaria
Czech Republic
Brno, Czech Republic
Hradec Kralove, Czech Republic
Praha, Czech Republic
Netherlands
Rotterdam, Netherlands
New Zealand
Christchurch, New Zealand
Palmerston North, New Zealand
Poland
Bialystok, Poland
Chorzow, Poland
Gdansk, Poland
Krakow, Poland
Lodz, Poland
Wroclaw, Poland
Singapore
Singapore, Singapore
Slovakia
Bratislava, Slovakia
South Africa
Johannesburg, South Africa
Ukraine
Dnipropetrovsk, Ukraine
Donetsk, Ukraine
Ivano-Frankivsk, Ukraine
Kyiv, Ukraine
Lviv, Ukraine
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Joe McIntosh Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01438840     History of Changes
Other Study ID Numbers: E5501-G000-302
Study First Received: September 19, 2011
Last Updated: March 31, 2014
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Chronic Immune Thrombocytopenia

Additional relevant MeSH terms:
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014