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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01054443
Recruitment Status : Terminated (The study objectives became unachievable as a result of the termination of 0913M0621)
First Posted : January 22, 2010
Last Update Posted : May 22, 2018
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )

Brief Summary:
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of S-888711 in the treatment of subjects with immune thrombocytopenia. Eligible subjects will be randomized into one of four treatment groups to receive S-888711 0.5 mg, 0.75 mg, or 1.0 mg or placebo.

Condition or disease Intervention/treatment Phase
Immune Thrombocytopenia (ITP) Drug: placebo to S-888711 Drug: S-888711 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2010
Actual Primary Completion Date : November 2010
Actual Study Completion Date : December 2010

Arm Intervention/treatment
Placebo Comparator: placebo Drug: placebo to S-888711

Experimental: 0.5 mg Drug: S-888711

Experimental: 0.75 mg Drug: S-888711

Experimental: 1.0 mg Drug: S-888711

Primary Outcome Measures :
  1. The primary efficacy endpoint is the proportion of responder subjects in each treatment group [ Time Frame: 6-weeks ]
    The responders were subjects with 1) achieved a platelet count of ≥ 50, 000/µL after 6 weeks of dosing 2) prematurely withdrawn due to a platelet count > 400,000/ µL prior to Day 42

Secondary Outcome Measures :
  1. Safety of S-888711 [ Time Frame: 6-weeks ]
  2. Pharmacokinetics (PK) profile of S-888711 using sparse PK sampling [ Time Frame: 6-weeks ]
  3. PK profile of S-888711 using serial PK sampling in a selected subset of subjects [ Time Frame: 6-weeks ]
  4. PK/PD relationship of S-888711 with respect to platelet count [ Time Frame: 6-weeks ]
  5. Impact of S-888711 on the incidence and severity of bleeding [ Time Frame: 6-weeks ]
  6. Pharmacodynamic (PD) effect of S-888711 on platelet count and markers of platelet function, such as endogeneous thrombopoietin (TPO) [ Time Frame: 6-weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  • PT and APTT within 20% of the upper limit of normal
  • 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/mm3
    • 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 IgM 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01054443

United States, California
Anaheim, California, United States, 92801
Los Angeles, California, United States, 90272
United States, District of Columbia
Washington, District of Columbia, United States, 20007
United States, Florida
Boynton Beach, Florida, United States, 33426
Jacksonville, Florida, United States, 32207
United States, Georgia
Atlanta, Georgia, United States, 30341
Riverdale, Georgia, United States, 30274
United States, Louisiana
Metairie, Louisiana, United States, 70006
United States, Maryland
Bethesda, Maryland, United States, 20817
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Missouri
Jefferson City, Missouri, United States, 65109
Kansas City, Missouri, United States, 64131
United States, New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
New York, New York, United States, 10021
New York, New York, United States, 10029
United States, Ohio
Cleveland, Ohio, United States, 44106
United States, Texas
San Antonio, Texas, United States, 78229
United States, Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi

Responsible Party: Shionogi Identifier: NCT01054443     History of Changes
Other Study ID Numbers: 0913M0621
First Posted: January 22, 2010    Key Record Dates
Last Update Posted: May 22, 2018
Last Verified: May 2018

Keywords provided by Shionogi Inc. ( Shionogi ):
Immune Thrombocytopenia (ITP)
Blood Platelet Disorders
Low Platelet Count
Hematologic Disease
Auto-immune thrombocytopenic Purpura
Relapsed Persistent or Chronic ITP
Idiopathic Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura (TTP)

Additional relevant MeSH terms:
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Skin Manifestations
Signs and Symptoms