Chronic Liver Disease, Thrombocytopenia
Conditions
Keywords
Elective invasive procedures
Brief summary
The primary purpose of this study is to compare the efficacy of lusutrombopag with placebo for the treatment of thrombocytopenia in patients with chronic liver disease who are undergoing elective invasive procedures.
Detailed description
The study consists of 3 periods: a screening period (up to 28 days prior to randomization), a treatment period of 7 days (Days 1 to 7 during which study drug is to be administered for 4 to 7 days), and a posttreatment period (through 28 days posttreatment). Once-daily treatment with lusutrombopag 3 mg or placebo is to commence on Day 1 and continue for up to 7 days. Platelet count is to be determined on Days 5, 6, and 7 prior to administration of study drug; if a participant meets the administration stopping criterion (ie, platelet count ≥ 50 × 10⁹/L with an increase of ≥ 20 × 10⁹/L from baseline), no additional dose of study drug is to be administered. The planned invasive procedure is to be performed in the posttreatment period between Days 9 and 14. Platelet count for determination of the need for platelet transfusion is to be determined on or after Day 8, but no more than 2 days prior to the invasive procedure; a platelet transfusion is required if the platelet count is \< 50 × 10⁹/L.
Interventions
DRUGLusutrombopag
Tablets for oral administration
DRUGPlacebo
Tablets for oral administration
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to understand the study and comply with all study procedures. 2. Willing to provide written informed consent prior to Screening. 3. Male or female. 4. 18 years of age or older at the time of signing informed consent. 5. Platelet count \< 50 × 10\^9/L at baseline on Day 1 prior to randomization. 6. Undergoing an elective invasive procedure. 7. In the opinion of the investigator, able to meet study requirements. 8. Male patients who are sterile or who agree to use an appropriate method of contraception (including use of a condom with spermicide) from Screening to completion of the Post-treatment Period. 9. Female patients who are not postmenopausal or surgically sterile need to agree to use a highly effective contraception (including contraceptive implant, injectable contraceptive, combination hormonal contraceptive \[including vaginal rings\], intrauterine contraceptive device or vasectomised partner) from Screening to completion of the Post-treatment Period. Barrier method with or without spermicide, double barrier contraception and oral contraceptive pill are insufficient methods on their own.
Exclusion criteria
1. Any of the following diseases: * hematopoietic tumor * aplastic anemia * myelodysplastic syndrome * myelofibrosis * congenital thrombocytopenia * drug-induced thrombocytopenia * generalized infection requiring treatment except for viral liver disease * immune thrombocytopenia. 2. History of splenectomy. 3. History of liver transplantation. 4. Any of the following at Screening: * hepatic encephalopathy uncontrolled by drugs * ascites uncontrolled by drugs. 5. Portal vein tumor embolism. 6. Known to be positive for the human immunodeficiency virus. 7. Past or present thrombosis or prothrombotic condition (e.g., cerebral infarction, myocardial infarction, angina pectoris, coronary artery stent placement, angioplasty, coronary artery bypass grafting, congestive heart failure \[New York Heart Association Grade III/IV\], arrhythmia known to increase the risk of thromboembolic events \[atrial fibrillation\], pulmonary thromboembolism, deep vein thrombosis, or disseminated intravascular coagulation syndrome). 8. History or evidence of any of the following diseases: * congenital thrombotic disease (eg, antithrombin deficiency, protein C deficiency, protein S deficiency, or coagulation factor \[Factor V Leiden\] mutation) * acquired thrombotic disease (eg, antiphospholipid antibody syndrome, paroxysmal nocturnal hemoglobinuria, hyperhomocysteinemia, or increased factor VIII) * Budd Chiari syndrome. 9. Portal vein thrombosis based on ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) within 28 days prior to randomization or a history of portal vein thrombosis. 10. Absence of hepatopetal blood flow in the main trunk of the portal vein as demonstrated by Doppler ultrasonography within 28 days prior to randomization. 11. History or evidence of disease associated with a risk of bleeding (e.g., coagulation factor deficiency or von Willebrand factor deficiency). 12. Bleeding score at randomization ≥ Grade 2 according to the World Health Organization (WHO) Bleeding Scale. 13. Any of the following drugs or therapies within 90 days prior to randomization: * anticancer drugs * interferon preparations * radiation therapy * exsanguination * other thrombopoietin receptor agonist * any investigational agent. 14. Any invasive procedure within 14 days prior to randomization. 15. Blood transfusion within 14 days prior to randomization. 16. Prior treatment with lusutrombopag (S-888711). 17. Pregnancy or lactation. 18. Known or suspected ongoing, active alcohol or substance abuse. Patients with a recent history who the investigator feels are able to comply with the study procedures and medications will be allowed to participate. 19. Considered ineligible by the investigator for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Required No Platelet Transfusion Prior to the Primary Invasive Procedure and No Rescue Therapy For Bleeding From Randomization Through 7 Days After the Primary Elective Procedure | From Randomization to 7 days after the invasive procedure, up to approximately 21 days. | Participants were considered as meeting the primary endpoint if all of the following conditions were satisfied: * Required no platelet transfusion from the date of randomization through at least 7 days after the primary invasive procedure * Did not receive the following rescue therapy for bleeding from the date of randomization through 7 days after the primary invasive procedure * Platelet preparations * Other blood preparations, including red blood cells and plasma * Volume expanders * Underwent an invasive procedure. Participants who received at least one platelet transfusion prior to the primary invasive procedure, received at least one rescue therapy for bleeding from the date of randomization through 7 days after the primary invasive procedure, discontinued from the study before undergoing the primary invasive procedure, or did not undergo an invasive procedure were considered as not meeting the primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Response | From Day 1 to the end of the posttreatment period, 35 days. | A response was defined as a platelet count of ≥ 50 × 10⁹/L with an increase of ≥ 20 × 10⁹/L from Baseline at any time during the study. Participants who met this response criterion only after platelet transfusion were considered as nonresponders. |
| Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L | From Day 1 to the end of the posttreatment period, 35 days. | The duration of the increase in platelet count was defined as the number of days during which the platelet count was maintained as ≥ 50 × 10⁹/L. |
| Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L by Platelet Transfusion Status | From Day 1 to the end of the posttreatment period, 35 days. | The duration of the increase in platelet count was defined as the number of days during which the platelet count was maintained as ≥ 50 × 10⁹/L. |
| Percentage of Participants Who Required Rescue Therapy for Bleeding During the Study | From Day 1 to the end of the possttreatment period, 35 days. | Participants who received rescue therapy for bleeding events during the study. Platelet preparations, other blood preparations (including red blood cells and plasma), and volume expanders were considered as rescue therapy for bleeding events. |
| Number of Participants With Specified Total Number of Platelet Transfusions | From Day 1 to the end of the posttreatment period, 35 days. | The number of transfusions administered to each patient were collected over the duration of the trial. The data are presented as the number of patients with the highest total number of transfusions followed by the next highest number of transfusions, etc. |
| Percentage of Participants Who Required no Platelet Transfusion During the Study | From Day 1 to end of the posttreatment period, 35 days. | Participants who did not undergo the invasive procedure were considered as having received platelet transfusion. |
| Number of Participants With Adverse Events (AEs) | From first dose of study drug to 28 days after the last dose, 35 days. | — |
| Maximum Plasma Concentration (Cmax) of Lusutrombopag | Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day). | — |
| Time to Maximum Plasma Concentration (Tmax) of Lusutrombopag | Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day). | — |
| Area Under the Plasma Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Lusutrombopag | Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day). | — |
| Apparent Total Clearance (CL/F) of Lusutrombopag | Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day). | — |
| Change From Baseline in Platelet Count Over Time | Baseline and Days 5, 6, 7, 8, 10, 12, 14, 17, 21, 28, and 35. | — |
Participant flow
Recruitment details
The study was conducted at 138 sites in 22 countries (Argentina, Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Republic of Korea, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, and United States of America).
Pre-assignment details
The study consisted of a screening period (up to 28 days), a treatment period of 7 days, and a posttreatment period (through 28 days posttreatment). Randomization was stratified by the primary invasive procedure (ie, liver ablation/coagulation or other invasive procedures) and baseline platelet count (\< 35 × 10⁹/L or ≥ 35 × 10⁹/L).
Participants by arm
| Arm | Count |
|---|---|
| Lusutrombopag Lusutrombopag 3 mg once daily for up to 7 days. | 108 |
| Placebo Placebo once daily for up to 7 days. | 107 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Posttreatment Period | Adverse Event | 3 | 1 |
| Posttreatment Period | Lost to Follow-up | 1 | 1 |
| Posttreatment Period | Other - Miscellaneous | 2 | 0 |
| Posttreatment Period | Withdrawal by Subject | 3 | 2 |
| Treatment Period | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Lusutrombopag |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 11.3 | 56.1 years STANDARD_DEVIATION 11 | 55.2 years STANDARD_DEVIATION 11.6 |
| Baseline Platelet Count < 35 × 10⁹/L | 74 Participants | 38 Participants | 36 Participants |
| Baseline Platelet Count ≥ 35 × 10⁹/L | 139 Participants | 68 Participants | 71 Participants |
| Baseline Platelet Count Missing | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 12 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 188 Participants | 95 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Planned Invasive Procedure Liver ablation/ coagulation | 12 Participants | 5 Participants | 7 Participants |
| Planned Invasive Procedure Other | 203 Participants | 102 Participants | 101 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 32 Participants | 17 Participants | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not provided | 6 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 171 Participants | 86 Participants | 85 Participants |
| Sex: Female, Male Female | 81 Participants | 38 Participants | 43 Participants |
| Sex: Female, Male Male | 134 Participants | 69 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 107 | 0 / 107 |
| other Total, other adverse events | 23 / 107 | 22 / 107 |
| serious Total, serious adverse events | 7 / 107 | 7 / 107 |
Outcome results
Primary
Percentage of Participants Who Required No Platelet Transfusion Prior to the Primary Invasive Procedure and No Rescue Therapy For Bleeding From Randomization Through 7 Days After the Primary Elective Procedure
Participants were considered as meeting the primary endpoint if all of the following conditions were satisfied: * Required no platelet transfusion from the date of randomization through at least 7 days after the primary invasive procedure * Did not receive the following rescue therapy for bleeding from the date of randomization through 7 days after the primary invasive procedure * Platelet preparations * Other blood preparations, including red blood cells and plasma * Volume expanders * Underwent an invasive procedure. Participants who received at least one platelet transfusion prior to the primary invasive procedure, received at least one rescue therapy for bleeding from the date of randomization through 7 days after the primary invasive procedure, discontinued from the study before undergoing the primary invasive procedure, or did not undergo an invasive procedure were considered as not meeting the primary endpoint.
Time frame: From Randomization to 7 days after the invasive procedure, up to approximately 21 days.
Population: All randomized participants (intent-to-treat population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lusutrombopag | Percentage of Participants Who Required No Platelet Transfusion Prior to the Primary Invasive Procedure and No Rescue Therapy For Bleeding From Randomization Through 7 Days After the Primary Elective Procedure | 64.8 percentage of participants |
| Placebo | Percentage of Participants Who Required No Platelet Transfusion Prior to the Primary Invasive Procedure and No Rescue Therapy For Bleeding From Randomization Through 7 Days After the Primary Elective Procedure | 29.0 percentage of participants |
p-value: <0.000195% CI: [24.9, 48.5]Cochran-Mantel-Haenszel
Secondary
Apparent Total Clearance (CL/F) of Lusutrombopag
Time frame: Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day).
Population: Participants in the intensive pharmacokinetic (PK) sampling group with at least 1 PK parameter estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lusutrombopag | Apparent Total Clearance (CL/F) of Lusutrombopag | 1.10 L/h | Geometric Coefficient of Variation 36.1 |
Secondary
Area Under the Plasma Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Lusutrombopag
Time frame: Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day).
Population: Participants in the intensive pharmacokinetic (PK) sampling group with at least 1 PK parameter estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lusutrombopag | Area Under the Plasma Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Lusutrombopag | 2737 ng*hr/mL | Geometric Coefficient of Variation 36.1 |
Secondary
Change From Baseline in Platelet Count Over Time
Time frame: Baseline and Days 5, 6, 7, 8, 10, 12, 14, 17, 21, 28, and 35.
Population: All randomized participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 6 | 5.1 * 10⁹/L | Standard Deviation 8.1 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 14 | 17.3 * 10⁹/L | Standard Deviation 19.3 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 21 | 9.8 * 10⁹/L | Standard Deviation 16 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 35 | -1.3 * 10⁹/L | Standard Deviation 6.2 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 7 | 4.7 * 10⁹/L | Standard Deviation 7.9 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 5 | 1.1 * 10⁹/L | Standard Deviation 6.5 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 8 | 7.7 * 10⁹/L | Standard Deviation 9.5 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 28 | 1.7 * 10⁹/L | Standard Deviation 11.4 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 10 | 12.6 * 10⁹/L | Standard Deviation 10.6 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 17 | 17.1 * 10⁹/L | Standard Deviation 23.4 |
| Lusutrombopag | Change From Baseline in Platelet Count Over Time | Day 12 | 15.4 * 10⁹/L | Standard Deviation 12.3 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 10 | 36.7 * 10⁹/L | Standard Deviation 24.1 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 21 | 20.9 * 10⁹/L | Standard Deviation 20.3 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 28 | 12.4 * 10⁹/L | Standard Deviation 18.8 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 14 | 33.5 * 10⁹/L | Standard Deviation 19.9 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 6 | 13.6 * 10⁹/L | Standard Deviation 15.7 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 12 | 37.0 * 10⁹/L | Standard Deviation 18.5 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 17 | 27.2 * 10⁹/L | Standard Deviation 21.1 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 5 | 10.4 * 10⁹/L | Standard Deviation 12.5 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 8 | 27.4 * 10⁹/L | Standard Deviation 21.5 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 35 | 9.4 * 10⁹/L | Standard Deviation 19.3 |
| Placebo | Change From Baseline in Platelet Count Over Time | Day 7 | 20.6 * 10⁹/L | Standard Deviation 16.8 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 21 | 2.5 * 10⁹/L | Standard Deviation 9 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 5 | 0.4 * 10⁹/L | Standard Deviation 6.6 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 6 | -0.6 * 10⁹/L | Standard Deviation 7 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 7 | 0.0 * 10⁹/L | Standard Deviation 7.7 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 8 | -0.1 * 10⁹/L | Standard Deviation 5.2 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 12 | 3.1 * 10⁹/L | Standard Deviation 9.5 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 14 | 4.0 * 10⁹/L | Standard Deviation 11.8 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 17 | 1.9 * 10⁹/L | Standard Deviation 9 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 28 | 2.0 * 10⁹/L | Standard Deviation 8.9 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 35 | 0.7 * 10⁹/L | Standard Deviation 9.1 |
| Placebo With Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 10 | 2.1 * 10⁹/L | Standard Deviation 11 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 10 | 12.7 * 10⁹/L | Standard Deviation 20.6 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 21 | 13.2 * 10⁹/L | Standard Deviation 20.7 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 8 | 7.3 * 10⁹/L | Standard Deviation 13.5 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 7 | 6.7 * 10⁹/L | Standard Deviation 12.9 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 35 | 6.0 * 10⁹/L | Standard Deviation 15.9 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 28 | 10.1 * 10⁹/L | Standard Deviation 17.6 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 6 | 6.7 * 10⁹/L | Standard Deviation 12.4 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 5 | 6.1 * 10⁹/L | Standard Deviation 11.8 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 17 | 17.0 * 10⁹/L | Standard Deviation 27.7 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 14 | 12.8 * 10⁹/L | Standard Deviation 28.1 |
| Placebo Without Platelet Transfusion | Change From Baseline in Platelet Count Over Time | Day 12 | 14.8 * 10⁹/L | Standard Deviation 24 |
Secondary
Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L
The duration of the increase in platelet count was defined as the number of days during which the platelet count was maintained as ≥ 50 × 10⁹/L.
Time frame: From Day 1 to the end of the posttreatment period, 35 days.
Population: All randomized participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lusutrombopag | Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L | 15.11 days |
| Placebo | Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L | 0.98 days |
p-value: 0.0002van Elteren test
Secondary
Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L by Platelet Transfusion Status
The duration of the increase in platelet count was defined as the number of days during which the platelet count was maintained as ≥ 50 × 10⁹/L.
Time frame: From Day 1 to the end of the posttreatment period, 35 days.
Population: All randomized participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lusutrombopag | Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L by Platelet Transfusion Status | 1.73 days |
| Placebo | Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L by Platelet Transfusion Status | 19.21 days |
| Placebo With Platelet Transfusion | Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L by Platelet Transfusion Status | 0.00 days |
| Placebo Without Platelet Transfusion | Duration of Increase in Platelet Count to ≥ 50 × 10⁹/L by Platelet Transfusion Status | 8.86 days |
p-value: <0.0001Wilcoxon rank sum test
Secondary
Maximum Plasma Concentration (Cmax) of Lusutrombopag
Time frame: Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day).
Population: Participants in the intensive pharmacokinetic (PK) sampling group with at least 1 PK parameter estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Lusutrombopag | Maximum Plasma Concentration (Cmax) of Lusutrombopag | 157 ng/mL | Geometric Coefficient of Variation 34.7 |
Secondary
Number of Participants With Adverse Events (AEs)
Time frame: From first dose of study drug to 28 days after the last dose, 35 days.
Population: All randomized participants who received at least 1 dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lusutrombopag | Number of Participants With Adverse Events (AEs) | Serious adverse events | 7 Participants |
| Lusutrombopag | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| Lusutrombopag | Number of Participants With Adverse Events (AEs) | Adverse events with outcome of death | 3 Participants |
| Lusutrombopag | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 6 Participants |
| Lusutrombopag | Number of Participants With Adverse Events (AEs) | All adverse events | 51 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 13 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | All adverse events | 52 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse events | 7 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse events with outcome of death | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 1 Participants |
Secondary
Number of Participants With Specified Total Number of Platelet Transfusions
The number of transfusions administered to each patient were collected over the duration of the trial. The data are presented as the number of patients with the highest total number of transfusions followed by the next highest number of transfusions, etc.
Time frame: From Day 1 to the end of the posttreatment period, 35 days.
Population: All randomized participants (intent-to-treat population)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lusutrombopag | Number of Participants With Specified Total Number of Platelet Transfusions | No transfusions | 74 Participants |
| Lusutrombopag | Number of Participants With Specified Total Number of Platelet Transfusions | One transfusion | 34 Participants |
| Lusutrombopag | Number of Participants With Specified Total Number of Platelet Transfusions | Two transfusions | 0 Participants |
| Lusutrombopag | Number of Participants With Specified Total Number of Platelet Transfusions | Three transfusions | 0 Participants |
| Lusutrombopag | Number of Participants With Specified Total Number of Platelet Transfusions | Four transfusions | 0 Participants |
| Lusutrombopag | Number of Participants With Specified Total Number of Platelet Transfusions | Five transfusions | 0 Participants |
| Placebo | Number of Participants With Specified Total Number of Platelet Transfusions | Four transfusions | 0 Participants |
| Placebo | Number of Participants With Specified Total Number of Platelet Transfusions | No transfusions | 34 Participants |
| Placebo | Number of Participants With Specified Total Number of Platelet Transfusions | Three transfusions | 5 Participants |
| Placebo | Number of Participants With Specified Total Number of Platelet Transfusions | One transfusion | 61 Participants |
| Placebo | Number of Participants With Specified Total Number of Platelet Transfusions | Five transfusions | 1 Participants |
| Placebo | Number of Participants With Specified Total Number of Platelet Transfusions | Two transfusions | 6 Participants |
Secondary
Percentage of Participants Who Required no Platelet Transfusion During the Study
Participants who did not undergo the invasive procedure were considered as having received platelet transfusion.
Time frame: From Day 1 to end of the posttreatment period, 35 days.
Population: All randomized participants (intent-to-treat population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lusutrombopag | Percentage of Participants Who Required no Platelet Transfusion During the Study | 63.0 percentage of participants |
| Placebo | Percentage of Participants Who Required no Platelet Transfusion During the Study | 29.0 percentage of participants |
p-value: <0.000195% CI: [22.8, 46.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Required Rescue Therapy for Bleeding During the Study
Participants who received rescue therapy for bleeding events during the study. Platelet preparations, other blood preparations (including red blood cells and plasma), and volume expanders were considered as rescue therapy for bleeding events.
Time frame: From Day 1 to the end of the possttreatment period, 35 days.
Population: All randomized participants (intent-to-treat population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lusutrombopag | Percentage of Participants Who Required Rescue Therapy for Bleeding During the Study | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Required Rescue Therapy for Bleeding During the Study | 1.9 percentage of participants |
Secondary
Percentage of Participants With a Response
A response was defined as a platelet count of ≥ 50 × 10⁹/L with an increase of ≥ 20 × 10⁹/L from Baseline at any time during the study. Participants who met this response criterion only after platelet transfusion were considered as nonresponders.
Time frame: From Day 1 to the end of the posttreatment period, 35 days.
Population: All randomized participants (intent-to-treat population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lusutrombopag | Percentage of Participants With a Response | 64.8 percentage of participants |
| Placebo | Percentage of Participants With a Response | 13.1 percentage of participants |
p-value: <0.000195% CI: [42, 62.9]Cochran-Mantel-Haenszel
Secondary
Time to Maximum Plasma Concentration (Tmax) of Lusutrombopag
Time frame: Day 5, predose and 2, 4, 6, 8, 24, and 48 hours post-dose (24 and 48 hours post-dose = Day 6 and Day 7 prior to dose on that day).
Population: Participants in the intensive pharmacokinetic (PK) sampling group with at least 1 PK parameter estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lusutrombopag | Time to Maximum Plasma Concentration (Tmax) of Lusutrombopag | 5.95 hours |