Trial record 12 of 270 for:    Thrombocytopenia: Clinical Trials

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.
(Data not entered)
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01433978
First received: September 13, 2011
Last updated: March 10, 2016
Last verified: February 2016
  Purpose

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).


Condition Intervention Phase
Idiopathic Thrombocytopenic Purpura
Drug: Eltrombopag
Drug: Avatrombopag
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: 23
Study Start Date: April 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Avatrombopag (Core Study)
Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, once daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug.
Drug: Avatrombopag
Other Names:
  • E5501
  • Avatrombopag maleate
Active Comparator: Eltrombopag (Core Study)
Eltrombopag was administered orally as 25 mg, 50 mg, or 75 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 50 mg eltrombopag once daily and they were allowed to have their dose titrated up (maximum dose of 75 mg eltrombopag) or down (minimum dose of 25 mg eltrombopag) depending on their response to study drug.
Drug: Eltrombopag
Other Names:
  • Promacta
  • Revolade
Experimental: Avatrombopag (Open-label Extension)
Participants who met the eligibility requirements for the Open-label Extension (OLE) Phase or who discontinued the Core Study early because of lack of treatment effect were eligible to continue into the OLE Phase for up to 104 weeks of open-label avatrombopag therapy. Participants entering the OLE from the Core Study received a starting dose of open-label avatrombopag that was determined by the last dose of study drug at the End of Treatment (EOT) Visit (Visit 22) of the Core Study. Participants who discontinued the Core Study early because of lack of treatment effect and entered the OLE received open-label avatrombopag at a starting dose of 20 mg once daily of open-label avatrombopag.
Drug: Avatrombopag
Other Names:
  • E5501
  • Avatrombopag maleate

Detailed Description:
The study consisted of three phases: Prerandomization, Randomization (Core Study) and Extension Phase. Participants 18 years of age and over, who meet all the eligibility requirements, were randomized into the study. It was required that splenectomized participants made up at least 35% of the study population and no single platelet count was greater than 35x10^9/L. Participants were centrally stratified at randomization by splenectomy status, baseline platelet count, and use of concomitant ITP medication at baseline and were randomized to receive either double-blind avatrombopag or eltrombopag in a 1:1 ratio. Participants received blinded therapy at a starting dose of 20 mg avatrombopag once daily or 50 mg eltrombopag once daily. Participants were allowed to have their dose titrated up (maximum dose 40 mg avatrombopag and 75 mg for eltrombopag) or down (minimum dose 5 mg for avatrombopag and 25 mg for eltrombopag) depending on their response to study drug. The goal of dose modification was 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 duration of treatment in the Core study and the Extension Phase is approximately 26 and 104 weeks, respectively.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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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

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01433978     History of Changes
Other Study ID Numbers: E5501-G000-305 
Study First Received: September 13, 2011
Last Updated: March 10, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 27, 2016