- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01054443
A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Anaheim, California, United States, 92801
- Investigator
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Los Angeles, California, United States, 90272
- Investigator
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District of Columbia
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Washington, District of Columbia, United States, 20007
- Investigator
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Florida
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Boynton Beach, Florida, United States, 33426
- Investigator
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Jacksonville, Florida, United States, 32207
- Investigator
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Georgia
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Atlanta, Georgia, United States, 30341
- Investigator
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Riverdale, Georgia, United States, 30274
- Investigator
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Louisiana
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Metairie, Louisiana, United States, 70006
- Investigator
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Maryland
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Bethesda, Maryland, United States, 20817
- Investigator
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Investigator
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Missouri
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Jefferson City, Missouri, United States, 65109
- Investigator
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Kansas City, Missouri, United States, 64131
- Investigator
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New Jersey
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New Brunswick, New Jersey, United States, 08903
- Investigator
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New York
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New York, New York, United States, 10021
- Investigator
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New York, New York, United States, 10029
- Investigator
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Ohio
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Cleveland, Ohio, United States, 44106
- Investigator
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Texas
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San Antonio, Texas, United States, 78229
- Investigator
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Utah
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Salt Lake City, Utah, United States, 84132
- Investigator
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Washington
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Seattle, Washington, United States, 98109
- Investigator
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Participants received placebo tablets orally once a day for 42 days.
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Tablet
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Experimental: Lusutrombopag 0.5 mg
Participants received 0.5 mg lusutrombopag orally once a day for 42 days.
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Tablet
Other Names:
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Experimental: Lusutrombopag 0.75 mg
Participants received 0.75 mg lusutrombopag orally once a day for 42 days.
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Tablet
Other Names:
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Experimental: Lusutrombopag 1.0 mg
Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
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Tablet
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With a Response
Time Frame: Week 6
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Responders were participants with one of the following:
Participants were counted as non-responders if any of the following conditions held:
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Week 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Platelet Count at Week 6
Time Frame: Baseline and Week 6
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Baseline and Week 6
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Duration of Response
Time Frame: 6 weeks
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Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the treatment period.
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6 weeks
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Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Time Frame: Week 6
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Week 6
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Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Time Frame: Week 6
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Week 6
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Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period,
Time Frame: 6 weeks
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Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality. For each participant, the most severe WHO bleeding grade observed during the 6-week treatment period is reported. |
6 weeks
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Number of Participants Who Received Rescue Medication During the Treatment Period
Time Frame: 6 weeks
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6 weeks
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Number of Participants With Adverse Events (AEs)
Time Frame: 6 weeks
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An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug. |
6 weeks
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Lusutrombopag Plasma Concentration
Time Frame: Days 8, 22, and 36, after dosing
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Plasma concentrations of lusutrombopag were determined using a validated liquid chromatography mass spectrometry method.
The lower limit of quantification (LOQ) for the plasma assay for lusutrombopag was 0.1 ng/mL.
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Days 8, 22, and 36, after dosing
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Plasma Concentration of Metabolite S-888711 Deshexyl
Time Frame: Days 8, 22, and 36, after dosing
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Plasma concentrations of the major metabolite S-888711 deshexyl were determined using a validated liquid chromatography mass spectrometry method.
The lower limit of quantification (LOQ) for the plasma assay for S-888711 deshexyl was 0.1 ng/mL.
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Days 8, 22, and 36, after dosing
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Hematologic Diseases
- Hemorrhage
- Hemorrhagic Disorders
- Blood Coagulation Disorders
- Skin Manifestations
- Blood Platelet Disorders
- Thrombotic Microangiopathies
- Purpura, Thrombocytopenic
- Purpura
- Purpura, Thrombocytopenic, Idiopathic
- Thrombocytopenia
Other Study ID Numbers
- 0913M0621
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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