A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)

The primary objective of this study was to assess the efficacy of 3 dose levels of lusutrombopag (0.5 mg, 0.75 mg, and 1.0 mg) and placebo on platelet count.


Eligibility Criteria:
Inclusion Criteria:

* A signed and dated written informed consent
* Males and females ≥ 18 years of age
* All subjects must agree to use barrier contraception
* Diagnosis of ITP
* Subjects \> 60 years must have had a diagnostic bone marrow aspiration
* Relapsed persistent or chronic ITP status, with or without prior splenectomy (exception: in Hungary only splenectomized subjects will be enrolled), after having failed at least 1 prior ITP therapy (excluding TPO agonists) and have a platelet count \< 30,000/μL if not taking medications or \< 50,000/μL despite concomitant steroids or other ITP therapies, such as danazol or immunosuppressive drugs
* Subjects receiving steroid therapy must be on a stable dose
* Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN)
* Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed. The dosages of all these medications must be stable for at least 4 weeks prior to Visit 1 (Day 1)

Exclusion Criteria:

* History of clinically important hemorrhagic clotting disorder
* Females who are pregnant, lactating, or taking oral contraceptives
* History of alcohol/drug abuse or dependence within 1 year
* Use of the following drugs or treatment prior to Visit 1 (Day 1):

  * Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy;
  * Within 8 weeks - rituximab
  * Within 2 weeks - platelet transfusions or plasmapheresis treatment
  * Within 4 weeks - use of anti-platelet or anti-coagulant drugs
  * Within 1 week - Rho(D) immune globulin or intravenous immunoglobulin
* History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Screening
* Splenectomy within 4 weeks prior to Screening
* Clinically significant laboratory abnormalities

  * Hemoglobin \< 10.0 g/dL for men or women, not clearly related to ITP
  * Absolute neutrophil count \< 1000/mm\^3
  * Abnormal peripheral blood smear
  * Total bilirubin \> 1.5 x upper limit of normal
  * Alanine aminotransferase (ALT) \> 1.5 x upper limit of normal
  * Aspartate aminotransferase (AST) \> 1.5 x upper limit of normal
  * Creatinine \> 1.5 x upper limit of normal
  * Human immunodeficiency virus (HIV) positive
  * Hepatitis A immunoglobulin M antibody (IgM HAV) positive, hepatitis B surface antigen (HbsAg) or hepatitis C antibody (HCV) positive
  * Thyroid stimulating hormone (TSH) \> 1.5 x upper limit of normal
  * Free thyroxine (T4) \> 1.5 x upper limit of normal
* Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 \[AKR-501\] or LGD-4665) within 4 weeks prior to Screening
* Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 \[AKR-501\] or LGD-4665)
* Exposure to an investigative medication within the past 30 days