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 | LLT |
E.1.2 | Classification code | 10008953 |
E.1.2 | Term | Chronic liver disease |
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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/μL) 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 |
Evaluate the effect of eltrombopag on the proportion of subjects with bleeding prior to, during & up to 7 days following elective invasive procedures. Evaluate the safety & tolerability of eltrombopag when given once daily to thrombocytopenic subjects with chronic liver disease prior to, during & following elective invasive procedures. Demonstrate the ability of eltrombopag compared to placebo, to reduce the number of platelet transfusions given prior to, during & up to 4 weeks (30 days) following the elective invasive procedures in subjects with chronic liver disease & a baseline platelet count <50,000/μL. Evaluate the effect of eltrombopag on medical resource utilisation & platelet counts in subjects with chronic liver disease & a baseline platelet count <50,000/μL prior to, during & up to 4 weeks (30 days) following elective invasive procedures. Describe the pharmacokinetics (PK) of eltrombopag & explore the relationship between the PK & relevant safety & efficacy endpoints. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Male and female subjects, ≥18 years of age with chronic liver disease. 2. Child-Pugh score of 12 or less 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/μL. 6. A baseline serum sodium level >130mEq/L. 7. Haemoglobin concentration >8g/dL stable for at least one month. 8. A female is eligible to enter and participate in the study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who: • Has had a hysterectomy • Has had a bilateral oophorectomy (ovariectomy) • Has had a bilateral tubal ligation • Is post-menopausal (demonstrate total cessation of menses for greater than one year) Childbearing potential, has a negative urine and/or serum pregnancy test at screening, and within the 24 hour period prior to the first dose of investigational product and uses one of the following acceptable methods of contraception: • Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical study, and for 28 days after completion or premature discontinuation from the study to account for the elimination of the study drug (minimum of 5 half-lives). • Any intrauterine device (IUD) with a documented failure rate of less than 1% per year. • Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide). • Male partner who is sterile (diagnosed by a qualified medical professional) prior to the female subject’s study entry and is the sole sexual partner for that female. • Oral contraceptive (either combined or progesterone only). • Any other contraceptive method with a documented failure rate of <1% per year. 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 |
Subjects meeting any of the following criteria must not be enrolled in the study: 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 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. 10. Previous participation in TPL104054. |
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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 <50,000μL) 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 | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
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 | 10 |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |