Study PMA112509, a Phase I/II Study of Eltrombopag in Thrombocytopenic Subjects with Advanced Myelodysplastic Syndrome (MDS) or secondary Acute Myeloid Leukemia after MDS (sAML/MDS)

INTERVENTION:

Product Name: Eltrombopag Product Code: SB497115 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

ELTROMBOPAG CAS Number: 496775‐61‐2 Current Sponsor code: SB497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Product Name: Eltrombopag Product Code: SB497115 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

ELTROMBOPAG CAS Number: 496775‐61‐2 Current Sponsor code: SB497115 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 Product Name: Eltrombopag Product Code: SB497115 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

ELTROMBOPAG CAS Number: 496775‐61‐2 Current Sponsor code: SB497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use

CONDITION:

Advanced Myelodysplastic Syndrome (MDS) or secondary Acute Myeloid Leukemia after MDS ; MedDRA version: 12.0 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome

PRIMARY OUTCOME:

Main Objective: To evaluate the safety and tolerability of eltrombopag when administered to subjects with advanced MDS, sAML/MDS or de novo AML with 10‐50% bone marrow blasts. Primary end point(s): Safety and tolerability parameters including non‐hematological laboratory Grade 3/Grade 4 toxicities, change in bone marrow blast counts from baseline and adverse events reporting. Secondary Objective: To evaluate the effect of eltrombopag on platelet counts.; ; To evaluate the effect of eltrombopag on the need for platelet transfusions.; ; To evaluate the effect of eltrombopag on the duration of platelet transfusion independence.; ; To evaluate the effect of eltrombopag on bleeding events.; ; To evaluate the effect of eltrombopag on overall survival (OS).; ; To evaluate eltrombopag population pharmacokinetics.; ; ; ; ;

INCLUSION CRITERIA:

1. Adult subjects (18 years of age or older) with advanced MDS, sAML/MDS, or de novo AML with >=10% and <=50% blasts in bone marrow. Peripheral blood blast change over time should not be suggestive of highly proliferative disease (as judged by the investigator). 2. Subjects must be dependent on regular platelet transfusions or have a platelet count taken within the 4 weeks prior to randomization that is <30 Gi/L. 3. Subjects must be relapsed, refractory or ineligible to receive standard treatment options of azacitidine and decitabine and must be relapsed, refractory or ineligible to receive intensive chemotherapy or autologous/allogeneic stem cell transplantation. A subject may be considered relapsed/refractory to a standard treatment if it is discontinued due to lack of efficacy. For subjects ineligible for standard treatments, it is permissible to start one of these standard treatments while on study medication if the Investigator cons