An Open-label Safety Study of Lusutrombopag (S-888711) in Adults With Chronic Immune Thrombocytopenia (ITP)

An Open-label Safety Study of S-888711 in Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy

The primary objective of this study was to assess the long-term safety of lusutrombopag in the treatment of adults with relapsed persistent or chronic ITP with or without prior splenectomy.

This was an open-label, long-term safety study of lusutrombopag in the treatment of adults with relapsed persistent or chronic ITP with or without prior splenectomy. Patients who participate in this study must have completed the Phase 2 study 0913M0621 (NCT01054443), a double-blind, placebo controlled, parallel group study that evaluated the efficacy and safety lusutrombopag during which they either completed treatment or discontinued treatment due to a platelet count > 400,000/μL.

Inclusion Criteria:

• Subjects who previously participated in Study 0913M0621 (NCT01054443) and who completed treatment or discontinued treatment due to a platelet count > 400,000/μL and continued to meet all inclusion criteria of the previous study, listed below, including platelet counts < 50,000/μL were eligible for study participation. For the purpose of this study, initial screening visit and all prestudy time period refer to Study 0913M0621.
• 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
• Subjects receiving steroid therapy must be on a stable dose for at least 2 weeks prior to Screening
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN) at Screening
• Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed

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 1 week - Rho(D) immune globulin or intravenous immunoglobulin;
  • Within 2 weeks - plasmaphoresis treatment;
  • Within 4 weeks - use of anti-platelet or anti-coagulant drugs;
  • Within 8 weeks - rituximab;
  • Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy;

• History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Initial Screening

• Splenectomy within 4 weeks prior to Initial Screening

• Clinically significant laboratory abnormalities

  • Hemoglobin < 10.0 g/dL for men or women, not clearly related to ITP
  • Absolute neutrophil count < 1000/mm3
  • Abnormal peripheral blood smear with evidence of fibrosis confirmed by bonemarrow biopsy
  • 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 positive
  • Hepatitis A IgM antibody positive, hepatitis B surface antigen or hepatitis C antibody positive

• Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Initial Screening

• Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665)

• Exposure to an investigative medication within 4 weeks prior to the initial Screening Visit