Clinical trial NCT01054443: A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Immune Thrombocytopenia (ITP)
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)
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2010-01-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percentage of Participants With a Response
timeFrame: Week 6
Secondary outcomes:
measure: Change From Baseline in Platelet Count at Week 6
timeFrame: Baseline and Week 6
measure: Duration of Response
timeFrame: 6 weeks
measure: Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
timeFrame: Week 6
measure: Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
timeFrame: Week 6
measure: Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period,
timeFrame: 6 weeks
measure: Number of Participants Who Received Rescue Medication During the Treatment Period
timeFrame: 6 weeks
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 6 weeks
measure: Lusutrombopag Plasma Concentration
timeFrame: Days 8, 22, and 36, after dosing
measure: Plasma Concentration of Metabolite S-888711 Deshexyl
timeFrame: Days 8, 22, and 36, after dosing
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Investigator
state: California
city: Los Angeles
country: United States
facility: Investigator
state: California
city: Washington
country: United States
facility: Investigator
state: District of Columbia
city: Boynton Beach
country: United States
facility: Investigator
state: Florida
city: Jacksonville
country: United States
facility: Investigator
state: Florida
city: Atlanta
country: United States
facility: Investigator
state: Georgia
city: Riverdale
country: United States
facility: Investigator
state: Georgia
city: Metairie
country: United States
facility: Investigator
state: Louisiana
city: Bethesda
country: United States
facility: Investigator
state: Maryland
city: Boston
country: United States
facility: Investigator
state: Massachusetts
city: Jefferson City
country: United States
facility: Investigator
state: Missouri
city: Kansas City
country: United States
facility: Investigator
state: Missouri
city: New Brunswick
country: United States
facility: Investigator
state: New Jersey
city: New York
country: United States
facility: Investigator
state: New York
city: New York
country: United States
facility: Investigator
state: New York
city: Cleveland
country: United States
facility: Investigator
state: Ohio
city: San Antonio
country: United States
facility: Investigator
state: Texas
city: Salt Lake City
country: United States
facility: Investigator
state: Utah
city: Seattle
country: United States
facility: Investigator
state: Washington
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References: