Repeated Exposure to Eltrombopag in Adults With Idiopathic Thrombocytopenic Purpura (REPEAT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00424177
First received: January 17, 2007
Last updated: July 25, 2013
Last verified: May 2012
  Purpose

This open-label, repeat dosing study, TRA108057, will evaluate the efficacy, safety and tolerability of eltrombopag, when administered in a repeat, cyclic dosing schedule. The study will describe the effect of repeated (3 cycles), intermittent dosing of eltrombopag on the pharmacodynamics and durability of eltrombopag response as measured by the peripheral platelet counts.

For more information or to see if you qualify, please visit: http://www.itpstudy.com/gov


Condition Intervention Phase
Purpura, Thrombocytopaenic, Idiopathic
Drug: eltrombopag
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Repeat Dosing Study of Eltrombopag Olamine (SB-497115-GR) in Adult Subjects, With Chronic Idiopathic Thrombocytopenic Purpura (ITP)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Who Responded (Platelet Count >=50 Gi/L and >=2x Baseline) to Eltrombopag Treatment in Cycle 2 or Cycle 3 Given Participants Responded in Cycle 1 [ Time Frame: Day 42 of each cycle ] [ Designated as safety issue: No ]
    Complete blood count, platelet count by blood draw


Secondary Outcome Measures:
  • Number of Participants Who Responded (Platelet Count Greater Than or Equal to 50 Gi/L and at Least 2x Baseline) for at Least 80 Percent of Their On-therapy Assessments During Weeks 2-6. [ Time Frame: Up to 42 days of dosing ] [ Designated as safety issue: No ]
    CBC, platelet counts

  • Changes in Participants' Platelet Counts During 3 Cycles of Treatment [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Changes from baseline, during on-therapy periods of a cycle, during off-therapy periods of a cycle, and within 4 weeks of permanent discontinuation of eltrombopag treatment.

  • Number of Participants Who Required Rescue Medication [ Time Frame: Up to 3 cycles of treatment including follow-up visits following last dose of eltrombopag ] [ Designated as safety issue: No ]
    New idiopathic thrombocytopenic purpura (ITP) medication, increase dose of a concomitant ITP medication from baseline, platelet transfusion, and/or splenectomy

  • Change in Participants Anti-platelet Antibody Levels From Baseline Through Follow-up [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Change in participants' anti-platelet antibody levels was measured as the number of samples positive for at least 1 glycoprotein from baseline to follow-up. Serum glycoprotein-specific antigens: GPIIb/IIIa, Ib/IX, and Ia/IIa

  • Number of Participants With the Indicated Bleeding Signs and Symptoms Using the World Health Organization Bleeding Scale [ Time Frame: Baseline, on-treatment visits (Weeks 1-6), off-treatment visits (Weeks 1-4) ] [ Designated as safety issue: No ]
    World health Organization (WHO) Bleeding Scale Grade 0 = no bleeding, Grade 1 = petechiae, Grade 2 = mild blood loss, Grade 3 = gross blood loss, Grade 4 = debilitating blood loss.

  • Number of Participants With the Indicated Bleeding Signs and Symptoms Using the ITP Bleeding Score [ Time Frame: Baseline, on-treatment visits (Weeks 1-6), off-treatment visits (Weeks 1-4) ] [ Designated as safety issue: No ]
    ITP Bleeding Score: Grade 0 = no bleeding, Grade 1 = mild bleeding, Grade 2 = severe bleeding


Enrollment: 66
Study Start Date: March 2007
Study Completion Date: November 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: eltrombopag Drug: eltrombopag
experimental
Other Name: eltrombopag

  Eligibility

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

Inclusion Criteria:

Subjects eligible for enrolment in the study must meet all of the following criteria:

  • Subject has signed and dated a written inform consent.
  • Adults (≥18 years) diagnosed with chronic ITP according to the American Society of Hematology/British Committee for Standards in Hematology guidelines, and a platelet count between ≥20 Gi/L and ≤50 Gi/L on Day 1 (or within 24 hours prior to dosing on Day 1). In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia (e.g. pseudothrombocytopenia, myelodysplasia). The physical examination should not suggest any disease which may cause thrombocytopenia other than ITP.
  • Subjects who have previously received one or more prior ITP therapies. Previous treatments for ITP include but are not limited to corticosteroids, immunoglobulins, azathioprine, danazol, cyclophosphamide and/or rituximab.
  • Subjects must have either initially responded (platelet count >100 Gi/L) to a previous ITP therapy or have had a bone marrow biopsy consistent with ITP within 3 years to rule out myelodysplastic syndromes or other causes of thrombocytopenia.
  • It is important to clearly differentiate the effect of eltrombopag on platelet count from the treatment effects of prior and concomitant ITP therapies. Therefore:

    1. Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 1 week prior to randomization and the platelet count must show a clear downward trend after the last treatment with immunoglobulins. Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to randomization, or clearly be ineffective.
    2. Subjects treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for a least 4 weeks prior to randomization. Subjects treated with cyclosporine A, mycophenolate mofetil or danazol must be receiving a dose that has been stable for at least 3 months prior to randomization.
  • Prothrombin time and activated partial thromboplastin time must be within 80 to 120% of normal range with no history of hypercoagulable state.
  • A complete blood count (CBC), within the reference range (including differential not indicative of a disorder other than ITP), with the following exceptions:
  • Platelet count between ≥20 Gi/L and ≤50 Gi/L on Day 1 (or within 24 hours of Day 1) is required for inclusion.
  • Hemoglobin: Subjects with hemoglobin levels between 10g/dL (100g/L) and the lower limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).
  • Absolute Neutrophil Count (ANC ) >1500/mL (1.5 x 10^9/L) is required for inclusion (elevated White Blood Cells/ANC above the reference range due to steroid treatment is acceptable).
  • The following clinical chemistries MUST NOT exceed the normal reference range by more than 20%: creatinine, Alanine aminotransferase, Aspartate aminotransferase, total bilirubin, total albumin and alkaline phosphatase.
  • Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal >1 year), or of childbearing potential and use of one of the following acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:

Complete abstinence from intercourse; Intrauterine device (IUD); Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide); Male partner is sterile prior to entry into the study and is the only partner of the female; Systemic contraceptives (combined or progesterone only).

  • Subject is able to understand and comply with protocol requirements and instructions and intends to complete the study as planned.

Exclusion Criteria:

A subject will NOT be eligible for inclusion in this study if any of the following criteria apply:

  • Any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
  • Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
  • Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), AND ≥ two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), 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.
  • Pre-existing cardiovascular disease (congestive heart failure, New York Heart Association Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec.
  • Female subjects who are nursing or pregnant (positive serum or urine b-human chorionic gonadotrophin pregnancy test) at screening or pre-dose on Day 1.
  • History of alcohol/drug abuse.
  • Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
  • Subject treated with drugs that affect platelet function (including but not limited to aspirin, clopidogrel and/or Non Steroidal Anti Inflammatory Drugs) or anti-coagulants for > 3 consecutive days within 2 weeks of the study start and until the end of the study.
  • History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
  • All subjects with secondary immune thrombocytopenia, including those with laboratory or clinical evidence of human immunodeficiency virus (HIV) infection, anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence for active hepatitis at the time of subject screening. If a potential subject has no clinical history that would support HIV infection or hepatitis infection, no further laboratory screening is necessary; however, standard medical practice would suggest further evaluation of patients who have risk factors for these infections.
  • Previous participation in a clinical study with eltrombopag.
  • Subjects planning to have cataract surgery.
  • In France, a subject is neither affiliated with nor a beneficiary of a social security category.
  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: NCT00424177

Locations
Germany
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Berlin, Germany, 13353
Russian Federation
GSK Investigational Site
Moscow, Russian Federation, 125167
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00424177     History of Changes
Other Study ID Numbers: TRA108057
Study First Received: January 17, 2007
Results First Received: June 23, 2009
Last Updated: July 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
idiopathic thrombocytopenic purpura
ITP
thrombocytopenia
platelets

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

ClinicalTrials.gov processed this record on August 25, 2014