Immune Thrombocytopenia (ITP)
Conditions
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)
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.
Interventions
DRUGPlacebo
Tablet
DRUGLusutrombopag
Tablet
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Response | Week 6 | Responders were participants with one of the following: 1. achieved a platelet count of ≥ 50,000 cells/µL after 6 weeks of dosing; or 2. 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
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 6 weeks | 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 | Week 6 | — |
| Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | Week 6 | — |
| Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | 6 weeks | 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. |
| Change From Baseline in Platelet Count at Week 6 | Baseline and Week 6 | — |
| Number of Participants With Adverse Events (AEs) | 6 weeks | 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 | Days 8, 22, and 36, after dosing | 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 | Days 8, 22, and 36, after dosing | 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. |
| Number of Participants Who Received Rescue Medication During the Treatment Period | 6 weeks | — |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized in a 1:1:1:1 ratio to 1 of 4 treatment groups to receive lusutrombopag 0.5 mg, 0.75 mg, or 1.0 mg or placebo administered orally once daily for 42 days. Randomization was stratified according to Screening platelet count (\< 30,000 cells/μL or ≥ 30,000 cells/μL to \< 50,000 cells/μL).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablets orally once a day for 42 days. | 5 |
| Lusutrombopag 0.5 mg Participants received 0.5 mg lusutrombopag orally once a day for 42 days. | 5 |
| Lusutrombopag 0.75 mg Participants received 0.75 mg lusutrombopag orally once a day for 42 days. | 5 |
| Lusutrombopag 1.0 mg Participants received 1.0 mg lusutrombopag orally once a day for 42 days. | 5 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Lusutrombopag 1.0 mg | Lusutrombopag 0.75 mg | Lusutrombopag 0.5 mg |
|---|---|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 18.24 | 54.7 years STANDARD_DEVIATION 20.36 | 43.2 years STANDARD_DEVIATION 15.39 | 55.0 years STANDARD_DEVIATION 23.4 | 59.2 years STANDARD_DEVIATION 24.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 18 Participants | 5 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Platelet Count at Screening < 30,000 cells /μL | 5 Participants | 19 Participants | 5 Participants | 4 Participants | 5 Participants |
| Platelet Count at Screening ≥ 30,000 cells/μL to < 50,000 cells/μL | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 19 Participants | 5 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 4 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 1 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 4 / 5 | 5 / 5 | 5 / 5 | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 1 / 5 |
Outcome results
Primary
Percentage of Participants With a Response
Responders were participants with one of the following: 1. achieved a platelet count of ≥ 50,000 cells/µL after 6 weeks of dosing; or 2. 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
Population: The full analysis set included all randomized participants who received at least 1 dose of study drug and had a platelet count at Baseline and at least 1 platelet count after randomized study drug was taken.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Response | 0.0 percentage of participants |
| Lusutrombopag 0.5 mg | Percentage of Participants With a Response | 20.0 percentage of participants |
| Lusutrombopag 0.75 mg | Percentage of Participants With a Response | 0.0 percentage of participants |
| Lusutrombopag 1.0 mg | Percentage of Participants With a Response | 0.0 percentage of participants |
Comparison: The primary efficacy evaluation was to test if there was a linear relationship existing such that the higher the dose level, the larger the percentage of responders. The Cochran-Armitage trend test was employed by assigning the score 0, 0.5, 0.75, and 1 to placebo, lusutrombopag 0.5, 0.75, and 1.0 mg group, respectively, at the 0.025 level of significance (1-sided) to determine the test statistic for detecting a dose-response in the percentage of responders.p-value: 0.431Cochran-Armitage Trend Test
Secondary
Change From Baseline in Platelet Count at Week 6
Time frame: Baseline and Week 6
Population: Full analysis set participants who completed 6 weeks of treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Platelet Count at Week 6 | -3566.0 cells/µL | Standard Error 6400.05 |
| Lusutrombopag 0.5 mg | Change From Baseline in Platelet Count at Week 6 | 21978.1 cells/µL | Standard Error 6095.54 |
| Lusutrombopag 0.75 mg | Change From Baseline in Platelet Count at Week 6 | 8235.4 cells/µL | Standard Error 6465.37 |
| Lusutrombopag 1.0 mg | Change From Baseline in Platelet Count at Week 6 | -2809.4 cells/µL | Standard Error 6866.08 |
95% CI: [6202.8, 44885.3]
95% CI: [-8809.3, 32411.9]
95% CI: [-18794.3, 20307.5]
Secondary
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.
Time frame: 6 weeks
Population: Participants in the full analysis set with platelet counts ≥ 50,000 cells/μL at any time during the 6-week treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lusutrombopag 0.5 mg | Duration of Response | 0.399 percentage of days |
| Lusutrombopag 0.75 mg | Duration of Response | 0.426 percentage of days |
| Lusutrombopag 1.0 mg | Duration of Response | 0.103 percentage of days |
Secondary
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.
Time frame: Days 8, 22, and 36, after dosing
Population: Participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Lusutrombopag Plasma Concentration | Day 22 | 19.1 ng/mL | Geometric Coefficient of Variation 32.1 |
| Placebo | Lusutrombopag Plasma Concentration | Day 8 | 16.5 ng/mL | Geometric Coefficient of Variation 35.4 |
| Placebo | Lusutrombopag Plasma Concentration | Day 36 | 24.1 ng/mL | Geometric Coefficient of Variation 14.22 |
| Lusutrombopag 0.5 mg | Lusutrombopag Plasma Concentration | Day 22 | 19.6 ng/mL | Geometric Coefficient of Variation 32.2 |
| Lusutrombopag 0.5 mg | Lusutrombopag Plasma Concentration | Day 8 | 21.7 ng/mL | Geometric Coefficient of Variation 52.77 |
| Lusutrombopag 0.5 mg | Lusutrombopag Plasma Concentration | Day 36 | 21.1 ng/mL | Geometric Coefficient of Variation 36.33 |
| Lusutrombopag 0.75 mg | Lusutrombopag Plasma Concentration | Day 8 | 33.3 ng/mL | Geometric Coefficient of Variation 32.74 |
| Lusutrombopag 0.75 mg | Lusutrombopag Plasma Concentration | Day 36 | 30.4 ng/mL | Geometric Coefficient of Variation 40.28 |
| Lusutrombopag 0.75 mg | Lusutrombopag Plasma Concentration | Day 22 | 30.7 ng/mL | Geometric Coefficient of Variation 42.97 |
Secondary
Number of Participants Who Received Rescue Medication During the Treatment Period
Time frame: 6 weeks
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Received Rescue Medication During the Treatment Period | 1 Participants |
| Lusutrombopag 0.5 mg | Number of Participants Who Received Rescue Medication During the Treatment Period | 2 Participants |
| Lusutrombopag 0.75 mg | Number of Participants Who Received Rescue Medication During the Treatment Period | 3 Participants |
| Lusutrombopag 1.0 mg | Number of Participants Who Received Rescue Medication During the Treatment Period | 2 Participants |
Secondary
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.
Time frame: 6 weeks
Population: The safety population included all participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse events leading to withdrawal of study drug | 0 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 1 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event | 5 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Adverse Events (AEs) | Adverse events leading to withdrawal of study drug | 0 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event | 5 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 0 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Adverse Events (AEs) | Adverse events leading to withdrawal of study drug | 0 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Adverse Events (AEs) | Serious adverse events | 1 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Adverse Events (AEs) | Any treatment-emergent adverse event | 4 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Adverse Events (AEs) | Adverse events leading to withdrawal of study drug | 0 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 2 Participants |
Secondary
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.
Time frame: 6 weeks
Population: Full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 2 | 3 Participants |
| Placebo | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 3 | 0 Participants |
| Placebo | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 0 | 0 Participants |
| Placebo | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 1 | 2 Participants |
| Placebo | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 4 | 0 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 2 | 2 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 3 | 0 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 1 | 3 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 0 | 0 Participants |
| Lusutrombopag 0.5 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 4 | 0 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 2 | 1 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 0 | 2 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 1 | 2 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 3 | 0 Participants |
| Lusutrombopag 0.75 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 4 | 0 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 3 | 0 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 1 | 3 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 0 | 0 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 2 | 2 Participants |
| Lusutrombopag 1.0 mg | Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, | Grade 4 | 0 Participants |
Secondary
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
Population: Participants in the full analysis set who completed 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 0.0 percentage of participants |
| Lusutrombopag 0.5 mg | Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 60.0 percentage of participants |
| Lusutrombopag 0.75 mg | Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 20.0 percentage of participants |
| Lusutrombopag 1.0 mg | Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 0.0 percentage of participants |
Secondary
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
Population: Participants in the full analysis set who completed 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 0.0 percentage of participants |
| Lusutrombopag 0.5 mg | Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 40.0 percentage of participants |
| Lusutrombopag 0.75 mg | Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 0.0 percentage of participants |
| Lusutrombopag 1.0 mg | Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing | 0.0 percentage of participants |
Secondary
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.
Time frame: Days 8, 22, and 36, after dosing
Population: Participants who received at least 1 dose of study drug, with available data at each time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 36 | 0.1 ng/mL | Geometric Coefficient of Variation 28.15 |
| Placebo | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 22 | 0.1 ng/mL | Geometric Coefficient of Variation 23.87 |
| Placebo | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 8 | 0.1 ng/mL | Geometric Coefficient of Variation 68.1 |
| Lusutrombopag 0.5 mg | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 22 | 0.2 ng/mL | Geometric Coefficient of Variation 141.38 |
| Lusutrombopag 0.5 mg | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 8 | 0.3 ng/mL | Geometric Coefficient of Variation 176.69 |
| Lusutrombopag 0.5 mg | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 36 | 0.2 ng/mL | Geometric Coefficient of Variation 154.49 |
| Lusutrombopag 0.75 mg | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 8 | 0.2 ng/mL | Geometric Coefficient of Variation 50.41 |
| Lusutrombopag 0.75 mg | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 36 | 0.2 ng/mL | Geometric Coefficient of Variation 101.93 |
| Lusutrombopag 0.75 mg | Plasma Concentration of Metabolite S-888711 Deshexyl | Day 22 | 0.2 ng/mL | Geometric Coefficient of Variation 50.2 |