A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)
Condition: Immune Thrombocytopenia (ITP)
MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic
Intervention: Placebo; Lusutrombopag
Intervention description: Tablet; Tablet
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Blood Platelet Disorders; Immune Thrombocytopenia (ITP); Low Platelet Count; Thrombocytopaenia; S-888711; Splenectomy; Thrombopoiesis; Hematologic Disease; Auto-immune thrombocytopenic Purpura; Relapsed Persistent or Chronic ITP; Idiopathic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura (TTP)

Summary:

      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