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

This study has been terminated.
(The study objectives became unachievable as a result of the termination of 0913M0621)
Sponsor:
Information provided by:
Shionogi Inc.
ClinicalTrials.gov Identifier:
NCT01054443
First received: January 20, 2010
Last updated: September 13, 2011
Last verified: July 2011
  Purpose

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 Intervention Phase
Immune Thrombocytopenia (ITP)
Drug: placebo to S-888711
Drug: S-888711
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Shionogi Inc.:

Primary Outcome Measures:
  • The primary efficacy endpoint is the proportion of responder subjects in each treatment group [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]
    The responders were subjects with 1) achieved a platelet count of ≥ 50, 000/µL after 6 weeks of dosing 2) prematurely withdrawn due to a platelet count 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:
  • Safety of S-888711 [ Time Frame: 6-weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) profile of S-888711 using sparse PK sampling [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]
  • PK profile of S-888711 using serial PK sampling in a selected subset of subjects [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]
  • PK/PD relationship of S-888711 with respect to platelet count [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]
  • Impact of S-888711 on the incidence and severity of bleeding [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamic (PD) effect of S-888711 on platelet count and markers of platelet function, such as endogeneous thrombopoietin (TPO) [ Time Frame: 6-weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo Drug: placebo to S-888711
Tablet
Experimental: 0.5 mg Drug: S-888711
Tablet
Experimental: 0.75 mg Drug: S-888711
Tablet
Experimental: 1.0 mg Drug: S-888711
Tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01054443

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

No publications provided

Responsible Party: Shionogi Clinical Trials Administrator, Shionogi
ClinicalTrials.gov Identifier: NCT01054443     History of Changes
Other Study ID Numbers: 0913M0621
Study First Received: January 20, 2010
Last Updated: September 13, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Shionogi Inc.:
Immune Thrombocytopenia (ITP)
Thrombocytopaenia
Blood Platelet Disorders
Low Platelet Count
S-888711
Splenectomy
Thrombopoiesis
Hematologic Disease
Auto-immune thrombocytopenic Purpura
Relapsed Persistent or Chronic ITP
Idiopathic Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura (TTP)

Additional relevant MeSH terms:
Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on August 28, 2014