E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
thrombocytopenic subjects with Chronic Liver Disease Undergoing Elective Invasive Procedures |
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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 | HLT |
E.1.2 | Classification code | 10043555 |
E.1.2 | Term | Thrombocytopenias |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027681 |
E.1.2 | Term | Hepatic and hepatobiliary disorders NEC |
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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 demonstrate the ability of eltrombopag, compared to placebo to reduce the proportion of subjects with chronic liver disease and thrombocytopenia (platelets <50,000/mL) who receive platelet transfusions administered prior to, during and up to seven days following elective invasive procedures. |
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E.2.2 | Secondary objectives of the trial |
· To evaluate the effect of eltrombopag on the proportion of subjects with bleeding prior to, during and up to seven days following elective invasive procedures. · To evaluate the safety and tolerability of eltrombopag when administered once daily to thrombocytopenic subjects with chronic liver disease prior to, during and following elective invasive procedures. · To demonstrate the ability of eltrombopag compared to placebo, to reduce the number of platelet transfusions administered prior to, during and up to 4 weeks (30 days) following elective invasive procedures in subjects with chronic liver disease and a baseline platelet count <50,000/mL. · To evaluate the effect of eltrombopag on platelet counts in subjects with chronic liver disease and a baseline platelet count <50,000/mL prior to, during and up to 4 weeks (30 days) following elective invasive procedures. · To describe the pharmacokinetics (PK) of eltrombopag and explore the relationship between the PK and rele |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOGENETICA: Versione: Data: Titolo:ELEVATE: ELtrombopag EValuated for its Ability to overcome Thrombocytopenia and Enable procedures Obiettivi:Relationship between genetic variants and the pharmacokinetics of investigational product Relationship between genetic variants and safety and/or tolerability of investigational product Relationship between genetic variants and efficacy of investigational product
FARMACOCINETICA/FARMACODINAMICA: Versione: Data: Titolo:ELEVATE: ELtrombopag EValuated for its Ability to overcome Thrombocytopenia and Enable procedures Obiettivi:To describe the pharmacokinetics (PK) of eltrombopag and explore the relationship between the PK and relevant safety and efficacy endpoints.
ALTRI SOTTOSTUDI: studio della funzionalita' piastrinica
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E.3 | Principal inclusion criteria |
1. Male and female subjects, ≥18 years of age with chronic liver disease. 2. Child-Pugh score of 12 or less (See Appendix 3). 3. Model of End Stage Liver Disease (MELD) score of 24 or less. 4. Subjects who, in the opinion of the investigator, are appropriate candidates to undergo an elective invasive procedure and who require a platelet transfusion to manage the risk of bleeding associated with the procedure. 5. A baseline platelet count <50,000/mL. 6. A baseline serum sodium level >130mEq/L. 7. Haemoglobin concentration >8g/dL stable for at least one month. 9. Subject has no physical limitation to ingest and retain oral medication. 10. Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned. 11. Subject is able to provide signed and dated written informed consent. 12. In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. |
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E.4 | Principal exclusion criteria |
1. Subjects with a known hypersensitivity, intolerance or allergy to any of the ingredients in eltrombopag tablets. 2. Evidence of portal vein thrombosis on abdominal imaging (ultrasound with Doppler or appropriate MRI/CT imaging techniques) within 3 months of study start. 3. History of arterial or venous thrombosis, including Budd-Chiari Syndrome, AND ≥ two of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc.), hormone replacement therapy, systemic contraception therapy (containing oestrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer. 4. Any disease condition associated with current active WHO Grade 3 or 4 bleeding (See Appendix 4 and study procedures manual [SPM]). 5. Active infection requiring systemic antibiotic therapy. Prophylactic use of antibiotics is permitted. 6. Pregnant or nursing women. 7. Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication. 8. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts. 9. History of porphyria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
· Proportion of subjects with chronic liver disease and thrombocytopenia (platelets <50,000mL) who do not require a platelet transfusion prior to, during and up to seven days following elective invasive procedures. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
test di funzionalita' piastrinica |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |