A randomized, double-blind, placebo-controlled phase III study, to evaluate the efficacy, safety and tolerability of eltrombopag olamine (SB-497115-GR), a thrombopoietin receptor agonist, administered for 6 months as oral tablets once daily in adult subjects with previously treated chronic idiopathic thrombocytopenic purpura (ITP). - RAISE
- Conditions
- Idiopathic thrombocytopenic purpura (ITP)MedDRA version: 8.1 Level: LLT Classification code 10051057 Term: Idiopathic thrombocytopenia
- Registration Number
- EUCTR2006-000470-78-FR
- Lead Sponsor
- GlaxoSmithKline Research and Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1. Subject has signed and dated a written informed consent.
2. Adults (>18 years) diagnosed with chronic ITP according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003], and platelet count < 30,000/µL 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, myelofibrosis). The physical examination should be normal or at least not show signs suggestive of any disease other than ITP which may cause thrombocytopenia.
3. 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.
4. Subjects must have either initially responded (platelet count > 100,000/µL) to a previous ITP therapy or have had a bone marrow biopsy consistent with ITP within 3 years to rule out myelodysplasia or other causes of thrombocytopenia.
5. Previous therapy for ITP with immunoglobulins (IVIg and anti-D), and cyclophosphamide must have been completed at least 4 weeks prior to randomization. Treatment with rituximab must have been completed at least 12 weeks prior to randomization. Subjects who have had a splenectomy must have had the procedure performed at least 4 weeks prior to randomization.
6. Subjects treated with corticosteroids, must be receiving a dose that has been stable (dose change of +/- 5% is acceptable) for at least 1 month prior to randomization. Subjects treated with cyclosporine A, mycophenolate mofetil, azathioprine or danazol must be receiving a dose that has been stable (dose change of +/- 5% is acceptable) for at least 3 months prior randomization. The medication should be continued with a stable dose for the initial 6 weeks of study (See Section 9.1.2, Concomitant ITP Therapy”)
7. Normal prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT), no history of hypercoagulable state.
8. A complete blood count (CBC), within the reference range (including WBC differential not indicative of a disorder other than ITP), with the following exceptions:
• < 30,000 platelets/µL on Day 1 (or within 24 hours of Day 1) is required for inclusion,
• Hemoglobin: Subjects with hemoglobin levels between 10 g/dL (100 g/L) and the lower limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).
• ANC greater than 1500/µL (1.5 x 109/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
9. The following clinical chemistries MUST be within the normal reference range: creatinine, ALT, AST, total bilirubin, total albumin and alkaline phosphatase.
10. 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 oopherectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following acceptable methods of contraception from two weeks prior to administration of study me
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 a diagnosis other than ITP.
2. History of malignancy. NOTE: Patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
3. Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), AND at least two of the following risk factors: Factor V Leiden, hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer.
4. Pre-existing cardiac disease (including congestive heart failure, and arrhythmia requiring treatment), or clinically significant findings on resting 12-lead ECG at screening.
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. Subject treated with aspirin, aspirin-containing compounds, salicylates, anti-coagulants, quinine or non-steroidal anti-inflammatory (NSAIDs) for > 3 consecutive days within 2 weeks of the study start and until the end of the study.
9. Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements (See Section 9.1.1, for instructions on taking calcium and vitamin supplements), within 1 week of the study start. Subjects that consumed rosuvastatin or pravastatin within 1 week of the first dose of study medication and/or will require these medications during the 6 month dosing period.
10. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
11. All subjects with secondary immune thrombocytopenia, including those with laboratory or clinical evidence of 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.
12. Previous participation in a clinical study with eltrombopag.
13. Patients planning to have cataract surgery.
14. In France, a subject is neither affiliated with nor a beneficiary of a social security category.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method