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

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of S-888711 Tablets Administered Once-daily for 42 Days to Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy

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.

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