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

INTERVENTION:

Product Name: Eltrombopag Product Code: SB497115 Pharmaceutical Form: Tablet INN or Proposed

INN:

eltrombopag CAS Number: CASRN496775 Current Sponsor code: SB‐497115 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: Eltrombopag Product Code: SB497115 Pharmaceutical Form: Tablet INN or Proposed

INN:

eltrombopag CAS Number: CASRN496775 Current Sponsor code: SB‐497115 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use

CONDITION:

Idiopathic thrombocytopenic purpura (ITP) ; MedDRA version: 8.1 Level: LLT Classification code 10051057 Term: Idiopathic thrombocytopenia

PRIMARY OUTCOME:

Main Objective: To determine the efficacy of oral eltrombopag, when administered once daily, for 6 months duration, to previously treated adult subjects with chronic ITP Primary end point(s): The primary endpoint is the odds of achieving a platelet count at or 50,000/microL and = 400,000/microL during the 6 month treatment period, for subjects receiving eltrombopag relative to placebo Secondary Objective: • To assess ability of eltrombopag to prevent use of rescue treatment ; • To describe pharmacodynamics & durability of eltrombopag response; • To determine efficacy of oral eltrombopag, when administered once daily for 6 weeks ; • To assess safety & tolerability of eltrombopag when administered for 6 months; • To describe effect of eltrombopag on reduction of concomitant ITP medications from baseline; • To assess impact of eltrombopag on incidence & severity of bleeding symptoms of thrombocytopenia when administered once daily for 6 months ; • To assess impact of eltrombopag on health related QoL & patient reported outcomes;

EXPLORATORY OBJECTIVES:

; • To assess effect of administration of eltrombopag on anti‐platelet antibody levels; • To use proteomic analysis to identify proteins that may correlate with safety & tolerability and/or predict response to eltrombopag

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