Idiopathic thrombocytopenic purpura (ITP) MedDRA version: 8.1 Level: LLT Classification code 10021245 Term: Idiopathic thrombocytopenic purpura
Conditions
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject has signed and dated a written inform consent. 2. Adults (at least >18 years) diagnosed with chronic ITP according to the American Society of Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003], and a platelet count +/>20,000/microL and 100,000/microL) 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. 5. It is important to clearly differentiate the effect of eltrombopag on platelet count from the treatment effects of prior and concomitant ITP therapies. Therefore: a. 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. b. 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. 6. Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of normal range with no history of hypercoagulable state. 7. 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 >/=20,000/microL and 1500/microL (1.5 x 109/L) is required for inclusion (elevated WBC/ANC above the reference range due to steroid treatment is acceptable). 8. The following clinical chemistries MUST NOT exceed the normal reference range by more than 20%: creatinine, ALT, AST, total bilirubin, total albumin and alkaline phosphatase. 9. 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 compl
Exclusion criteria
Exclusion criteria: 1. 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). 2. Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy. 3. Any prior history of arterial or venous thrombosis AND two or more of the following risk factors: hereditary thrombophilic disorders (eg Factor V Leiden, ATIII deficiency, etc), hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer. 4. Pre-existing cardiac disease (congestive heart failure New York Heart Association (NYHA) Grade III/IV, (See Appendix 7), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec. 5. Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotrophin pregnancy test) at screening or pre-dose on Day 1. 6. History of alcohol/drug abuse. 7. Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication. 8. Subjects treated with drugs that affect platelet function (including but not limited to, aspirin, clopidogrel or NSAIDS) or anti-coagulants for >3 consecutive days within 2 weeks of the start and until the end of the study (Refer to Section 5.6.2., ‘Prohibited Medications and Non-Drug Therapies”). 9. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts. 10. 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. 11. Previous participation in a clinical study with eltrombopag. 12. Patients planning to have cataract surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of eltrombopag on platelet counts when administered during 3 cycles of repeated, intermittent treatment. A cycle is defined as up to 6 weeks on-treatment and up to 4-weeks off-treatment.;Secondary Objective: • To assess the number of subjects requiring rescue treatments over 3 cycles of therapy. • To assess the safety and tolerability of eltrombopag when administered over 3 cycles of therapy. • To assess anti-platelet antibody levels during the 3 cycles of eltrombopag treatment. • To assess the impact of eltrombopag on the incidence and severity of bleeding symptoms as measured by the WHO Bleeding Scale and ITP Bleeding Score over 3 cycles of therapy.;Primary end point(s): Consistency (durability of response) defined as the proportion of subjects who respond to eltrombopag treatment in Cycle 2 or 3 (given a response in Cycle 1). A response within a cycle is defined as a platelet count >/= 50,000/microL and at least 2x baseline (baseline is defined as Day 1 of each cycle) after up to 42 days of eltrombopag dosing. | — |
Countries
Germany, Spain, United Kingdom
Outcome results
None listed