Eltrombopag for the Treatment of Thrombocytopenia Due to Low- and Intermediate Risk Myelodysplastic Syndromes

Inclusion criteria

• Adult subjects (18 years of age or older) with low or intermediate-1 IPSS risk MDS and stable disease.
• Subjects must have a platelet count taken within the 4 weeks prior to randomization that is <30 Gi/L.
• Subjects must be ineligible or relapsed or refractory to receive other treatment options (such as azacitidine or lenalidomide) and must be ineligible to receive intensive chemotherapy or autologous/allogeneic stem cell transplantation.
• Subjects must have platelet count and platelet transfusion data available over a period of 8 weeks prior to randomization.
• During the 2 months prior to randomization, subjects must have a baseline Bone Marrow examination which includes cytomorphology and cytogenetics. Histopathology should be performed.
• Erythropoiesis-stimulating agents (ESAs) in anemic subjects or granulocyte colonystimulating factor (G-CSF) in subjects with severe neutropenia and recurrent infections are allowed during the study as per accepted standards. Subjects who enter the study on ESAs or G-CSF should continue at the same dose schedule until the optimal dose of study medication has been established.
• ECOG (Eastern Cooperative Oncology Group) Performance Status 0-3
• Subject is able to understand and comply with protocol requirements and instructions.
• Subject has signed and dated informed consent.
• Adequate baseline organ function defined by the criteria below:

total bilirubin (except for Gilbert's Syndrome) ≤ 1.5 x Upper Limit Normal Alanine aminotransferase and Aspartate aminotransferase ≤ 3 x Upper Limit Normal creatinine ≤ 2 x Upper Limit Normal albumin must not be below the lower limit of normal by more than 20%.

• Subject is practicing an acceptable method of contraception. Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal >1 year), or of childbearing potential and use of an highly effective method of contraception from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study.

Exclusion criteria

• MDS with intermediate-2 or high IPSS risk.
• History of treatment for cancer other than MDS with systemic chemotherapy and/or radiotherapy within the last 2 years.
• History of treatment with romiplostim or other Thrombopoietin receptor agonists.
• Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. persistent atrial fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block).
• BM fibrosis that leads to an inability to aspirate marrow for assessment.
• Peripheral monocytosis > 1000/uL prior to Day 1 of study medication.
• Leukocytosis >=25,000/uL prior to Day 1 of study medication.
• Female subjects who are nursing or pregnant (positive serum or urine Beta-human chorionic gonadotropin [B-hCG] pregnancy test) at screening or pre-dose on Day 1.
• Current alcohol or drug abuse.
• Treatment with an Investigational Product within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• Active and uncontrolled infections.
• Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).