Back to resultsA Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)
Primary Purpose
Immune Thrombocytopenia (ITP)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Lusutrombopag
Sponsored by
About this trial
This is an interventional treatment trial for Immune Thrombocytopenia (ITP) focused on measuring 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)
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
Sites / Locations
- Investigator
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
Lusutrombopag 0.5 mg
Lusutrombopag 0.75 mg
Lusutrombopag 1.0 mg
Arm Description
Participants received placebo tablets orally once a day for 42 days.
Participants received 0.5 mg lusutrombopag orally once a day for 42 days.
Participants received 0.75 mg lusutrombopag orally once a day for 42 days.
Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Outcomes
Primary Outcome Measures
Percentage of Participants With a Response
Responders were participants with one of the following:
achieved a platelet count of ≥ 50,000 cells/µL after 6 weeks of dosing; or
prematurely withdrawn due to a platelet count > 400,000 cells/µL prior to Day 42.
Participants were counted as non-responders if any of the following conditions held:
The above conditions were not satisfied;
They received rescue medications;
They satisfied the above conditions after receiving restricted medications during the treatment period;
They had achieved a platelet count of ≥ 50,000 cells/µL before Week 6 but not after Week 6; or
They withdrew for any reason other than a platelet count > 400,000 cells/µL.
Secondary Outcome Measures
Change From Baseline in Platelet Count at Week 6
Duration of Response
Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the treatment period.
Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period,
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.
Number of Participants Who Received Rescue Medication During the Treatment Period
Number of Participants With Adverse Events (AEs)
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.
Lusutrombopag Plasma Concentration
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.
Plasma Concentration of Metabolite S-888711 Deshexyl
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01054443
Brief Title
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
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated before the planned sample size was enrolled because results indicated that a higher dose was necessary to elicit an efficacy effect.
Study Start Date
March 18, 2010 (Actual)
Primary Completion Date
November 24, 2010 (Actual)
Study Completion Date
November 24, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shionogi
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo tablets orally once a day for 42 days.
Arm Title
Lusutrombopag 0.5 mg
Arm Type
Experimental
Arm Description
Participants received 0.5 mg lusutrombopag orally once a day for 42 days.
Arm Title
Lusutrombopag 0.75 mg
Arm Type
Experimental
Arm Description
Participants received 0.75 mg lusutrombopag orally once a day for 42 days.
Arm Title
Lusutrombopag 1.0 mg
Arm Type
Experimental
Arm Description
Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
Lusutrombopag
Other Intervention Name(s)
MULPLETA®, S-888711
Intervention Description
Tablet
Primary Outcome Measure Information:
Title
Percentage of Participants With a Response
Description
Responders were participants with one of the following:
achieved a platelet count of ≥ 50,000 cells/µL after 6 weeks of dosing; or
prematurely withdrawn due to a platelet count > 400,000 cells/µL prior to Day 42.
Participants were counted as non-responders if any of the following conditions held:
The above conditions were not satisfied;
They received rescue medications;
They satisfied the above conditions after receiving restricted medications during the treatment period;
They had achieved a platelet count of ≥ 50,000 cells/µL before Week 6 but not after Week 6; or
They withdrew for any reason other than a platelet count > 400,000 cells/µL.
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
Change From Baseline in Platelet Count at Week 6
Time Frame
Baseline and Week 6
Title
Duration of Response
Description
Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the treatment period.
Time Frame
6 weeks
Title
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
Title
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
Title
Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period,
Description
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.
Time Frame
6 weeks
Title
Number of Participants Who Received Rescue Medication During the Treatment Period
Time Frame
6 weeks
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
6 weeks
Title
Lusutrombopag Plasma Concentration
Description
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.
Time Frame
Days 8, 22, and 36, after dosing
Title
Plasma Concentration of Metabolite S-888711 Deshexyl
Description
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.
Time Frame
Days 8, 22, and 36, after dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shionogi Clinical Trials Administrator Clinical Support Help Line
Organizational Affiliation
Shionogi
Official's Role
Study Director
Facility Information:
Facility Name
Investigator
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Investigator
City
Los Angeles
State/Province
California
ZIP/Postal Code
90272
Country
United States
Facility Name
Investigator
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Investigator
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33426
Country
United States
Facility Name
Investigator
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Investigator
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30341
Country
United States
Facility Name
Investigator
City
Riverdale
State/Province
Georgia
ZIP/Postal Code
30274
Country
United States
Facility Name
Investigator
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Investigator
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Investigator
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Investigator
City
Jefferson City
State/Province
Missouri
ZIP/Postal Code
65109
Country
United States
Facility Name
Investigator
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Investigator
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Investigator
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Investigator
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Investigator
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Investigator
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Investigator
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Investigator
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)
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