E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic thrombocytopenic purpura ITP |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021245 |
E.1.2 | Term | Idiopathic thrombocytopenic purpura |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of oral eltrombopag, when administered once daily, for 6 months duration, to previously treated adult subjects with chronic ITP. |
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E.2.2 | Secondary objectives of the trial |
Assess the ability of eltrombopag to prevent the use of rescue treatment. To describe the pharmacodynamics and durability of eltrombopag response maintenance of an elevated blood platelet count .To determine the efficacy of oral eltrombopag, when administered once daily, for 6 weeks duration, to previously treated adult subjects with chronic ITP commitment to European Regulatory Agencies .To assess the safety and tolerability of eltrombopag when administered for 6 months to previously treated adult subjects with chronic ITP.To describe the effect of eltrombopag on reduction of concomitant ITP medications from baseline.To assess the impact of eltrombopag on the incidence and severity of bleeding symptoms of thrombocytopenia when administered once daily for 6 months in previously treated adult subject with chronic ITP. To assess the impact of eltrombopag on the health related quality of life and patient reported outcomes. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
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/ 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, 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/ L 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/ L 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 1500/ L 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 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 . 11. Subject is able to understand and comply with protocol requirements and instructions and intends to complete the study as planned. |
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E.4 | Principal 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 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 ; 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 -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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the odds of achieving a platelet count 50,000/ L and 400,000/ L during the 6 month treatment period, for subjects receiving eltrombopag relative to placebo. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |