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

Shionogi

Status and phase: Terminated; Phase 2

Conditions: Immune Thrombocytopenia (ITP)

Treatments: Drug: Lusutrombopag; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01054443

0913M0621

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo tablets orally once a day for 42 days.

Treatment:

Drug: Placebo

Lusutrombopag 0.5 mg

Experimental group

Description:

Participants received 0.5 mg lusutrombopag orally once a day for 42 days.

Treatment:

Drug: Lusutrombopag

Lusutrombopag 0.75 mg

Experimental group

Description:

Participants received 0.75 mg lusutrombopag orally once a day for 42 days.

Treatment:

Drug: Lusutrombopag

Lusutrombopag 1.0 mg

Experimental group

Description:

Participants received 1.0 mg lusutrombopag orally once a day for 42 days.

Treatment:

Drug: Lusutrombopag