A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Study to Evaluate the Safety and Efficacy of Eltrombopag to Reduce the Need for Platelet Transfusion in Thrombocytopenic Subjects with Chronic Liver Disease Undergoing Elective Invasive Procedures.

INTERVENTION:

Product Name: Eltrombopag Product Code: SB‐497115 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

Eltrombopag Current Sponsor code: SB‐497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 75‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use

CONDITION:

thrombocytopenic subjects with Chronic Liver Disease Undergoing Elective Invasive Procedures ; MedDRA version: 9.1 Level: HLT Classification code 10043555 Term: Thrombocytopenias ; MedDRA version: 9.1 Level: HLT Classification code 10027681 Term: Hepatic and hepatobiliary disorders

NEC PRIMARY OUTCOME:

Main Objective: · 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. 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. Secondary Objective: · 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

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 af