Thrombocytopenia Associated With Liver Disease
Conditions
Keywords
Thrombocytopenia, Chronic Liver Disease
Brief summary
This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag to treat adults with thrombocytopenia associated with liver disease. The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with liver disease prior to an elective procedure to reduce the need for platelet transfusions or any rescue procedure for bleeding due to procedural and post-procedural bleeding complications. Participants will be enrolled into 2 cohorts according to mean baseline platelet count and, within each baseline platelet count cohort will be further stratified by risk of bleeding associated with the elective procedure (low, moderate, or high) and hepatocellular carcinoma (HCC) status (Yes or No).
Detailed description
This study will consist of 3 phases: Prerandomization, Randomization, and a Follow-up Phase. The Prerandomization Phase includes one Screening Visit that will take place from Day -14 through Day -1; the Randomization Phase includes the Baseline Period, Treatment Period, and Procedure Day Period (5 to 8 days after last dose of study drug \[Study Day 10 to 13\]). The Follow-up Phase comprises 2 visits: 7 days post Procedure Day and 30 days after receiving the last dose of study drug. Permitted procedures include: Paracentesis; Thoracentesis; Gastrointestinal endoscopy with or without plans for biopsy, colonoscopy, polypectomy, or variceal banding; Liver biopsy; Bronchoscopy with or without plans for biopsy; Ethanol ablation therapy or chemoembolization for HCC; Vascular catheterization (including right side procedures in participants with pulmonary hypertension); Transjugular intrahepatic portosystemic shunt; Dental procedures; Renal biopsy; Biliary interventions; Nephrostomy tube placement; Radiofrequency ablation; and Laparoscopic interventions.
Interventions
60 mg avatrombopag (3 x 20 mg tablets)
60 mg placebo (3 x 20 mg matching placebo tablets)
40 mg avatrombopag (2 x 20 mg tablets)
40 mg placebo (2 x 20 mg matching placebo tablets)
Sponsors
Eisai Inc.
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
1. Participants greater than or equal to 18 years of age at Screening with chronic liver disease 2. Participants who have a mean baseline platelet count of less than 50 x 10\^9/L. Platelet counts must be measured on 2 separate occasions, during the Screening Period and at Baseline, and must be performed at least one day apart with neither platelet count greater than 60 x 10\^9/L. The mean of these 2 platelet counts (mean baseline platelet count) will be used for entry criteria and for assignment to the low or high baseline platelet count cohort. 3. Participants scheduled to undergo a permitted elective procedure who, in the opinion of the investigator, will require a platelet transfusion to address a risk of bleeding associated with the procedure unless there is a clinically significant increase in platelet count from baseline 4. Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening 5. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening 6. Provide written informed consent 7. Willing and able to comply with all aspects of the protocol
Exclusion criteria
1. Any history of arterial or venous thrombosis, including partial or complete thrombosis 2. Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening 3. Portal vein blood flow velocity rate \<10 centimeters/second at Screening 4. Hepatic encephalopathy that cannot be effectively treated 5. Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D 6. Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted. 7. Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil, and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban) within 7 days of Screening 8. Use of erythropoietin stimulating agents within 7 days of Screening 9. Interferon (IFN) use within 14 days of Screening 10. Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening 11. Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted. 12. Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start 13. Elective procedure performed prior to Visit 4 (Procedure Day) 14. Known to be human immunodeficiency virus positive 15. Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system) 16. Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome) 17. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.) 18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events \[eg, atrial fibrillation\], coronary artery stent placement, angioplasty, and coronary artery bypass grafting) 19. Females of childbearing potential who have had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a progesterone-only contraceptive implant/injection, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing. 20. Females who are lactating or pregnant at Screening or Baseline (as documented by a positive serum beta-human chorionic gonadotropin \[B-hCG\] test with a minimum sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 21. Post liver transplant subjects 22. Any participant who has previously received avatrombopag 23. Hypersensitivity to avatrombopag maleate or any of its excipients 24. Hemoglobin levels ≤ 8.0 or ≥ 18.0 g/dL for men and \> 15 for women at Screening, with hematocrit ≥ 54% for men and ≥ 45% for women 25. Current malignancy including solid tumors and hematologic malignancies (except HCC) 26. Any history of concomitant medical condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study 27. Currently enrolled in another clinical trial with any investigational drug or device within 30 days of Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure | Randomization (Visit 2), up to 7 Days following a scheduled procedure | Responders were defined as participants who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure. Participants with missing information due to early withdrawal or other reasons were conservatively considered as having received a transfusion in the analysis, (i.e. a Non-responder). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day | Day 10 to Day 13 (Visit 4) | Responders were defined as participants who achieved a platelet count greater than or equal to 50 x 10\^9/L on the procedure day. Participants missing a platelet count on the procedure day were conservatively considered as not achieving a platelet count of 50x10\^9/L in the analysis, (i.e. Non-responders). |
| Change From Baseline in Platelet Counts on Scheduled Procedure Day | Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4) | Last observation carried forward was used for participants with a missing platelet count on the scheduled procedure day. Platelet count was measured preprocedure and before any platelet transfusion. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure | Baseline (Visit 2) up to 7 days post scheduled procedure | The severity of bleeding events was assessed by the investigator (or appropriately delegated study site personnel) using the WHO bleeding scale. The WHO bleeding scale is a clinical investigator-assessed five-point scale with Grade 0 = No bleeding, Grade 1 = Petechial bleeding, Grade 2 = Mild blood loss (clinically significant), Grade 3 = Gross blood loss requires transfusion (severe), and Grade 4 = Debilitating blood loss, retinal or cerebral associated with fatality. Participants with missing information are considered as having a WHO bleeding score greater than or equal to 2 in the analysis. |
| Number of Participants Experiencing an Adverse Event | From date of first dose of study drug up to 30 days after the last dose of study drug, up to approximately 3 years and 2 months | Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious adverse events, including platelet transfusion-related complications; routine laboratory evaluation for hematology, serum chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); the performance of physical examinations; and Doppler sonography. AE severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Treatment-emergent adverse events (TEAEs) were defined as an AE that started on or after the date of first dose of study drug, up to 30 days after the last dose of study drug. Treatment-related AEs were considered by the investigator to be possibly or probably related to study drug. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Israel, Italy, Japan, Mexico, Romania, Russia, Spain, United States
Participant flow
Pre-assignment details
A total of 346 participants signed informed consent. Of these 346 participants, 142 were screen failures and 204 were randomized into the study. Of the 142 screen failures, 119 did not meet inclusion/exclusion criteria and 13 withdrew consent, 3 experienced an adverse event, 1 was lost to follow-up and 6 had other not specified reasons.
Participants by arm
| Arm | Count |
|---|---|
| 60 mg Placebo (Lower Baseline Platelet Count) Participants with a baseline platelet count of less than 40 x 10\^9/liters (L) took three 20 milligrams (mg) matching placebo tablets orally, once daily with a meal on Days 1 through 5. | 43 |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) Participants with a baseline platelet count of less than 40 x 10\^9/L took three 20 mg tablets (60 mg total) avatrombopag (2nd generation) orally, once daily with a meal on Days 1 through 5. | 70 |
| 40 mg Placebo (Higher Baseline Platelet Count) Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10\^9/L took two 20 mg matching placebo tablets orally, once daily with a meal on Days 1 through 5. | 33 |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) Participants with a baseline platelet count of greater than or equal to 40 to less than 50 x 10\^9/L took two 20 mg tablets (40 mg total) avatrombopag (2nd generation) orally, once daily with a meal on Days 1 through 5. | 58 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 1 | 1 |
| Overall Study | Other | 0 | 1 | 0 | 0 |
| Overall Study | Subject Choice | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 60 mg Placebo (Lower Baseline Platelet Count) | 60 mg Avatrombopag (Lower Baseline Platelet Count) | 40 mg Placebo (Higher Baseline Platelet Count) | 40 mg Avatrombopag (Higher Baseline Platelet Count) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 11.98 | 58.6 years STANDARD_DEVIATION 14.18 | 59.2 years STANDARD_DEVIATION 10.31 | 57.9 years STANDARD_DEVIATION 11.11 | 58.2 years STANDARD_DEVIATION 12.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 11 Participants | 7 Participants | 15 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 56 Participants | 25 Participants | 42 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 25 Participants | 8 Participants | 12 Participants | 55 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 3 Participants | 0 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 27 Participants | 40 Participants | 24 Participants | 40 Participants | 131 Participants |
| Sex: Female, Male Female | 16 Participants | 20 Participants | 16 Participants | 25 Participants | 77 Participants |
| Sex: Female, Male Male | 27 Participants | 50 Participants | 17 Participants | 33 Participants | 127 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 / 43 | 0 / 70 | 1 / 33 | 0 / 57 |
| other Total, other adverse events | 22 / 43 | 30 / 70 | 15 / 33 | 14 / 57 |
| serious Total, serious adverse events | 1 / 43 | 1 / 70 | 1 / 33 | 1 / 57 |
Outcome results
Primary
Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure
Responders were defined as participants who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure. Participants with missing information due to early withdrawal or other reasons were conservatively considered as having received a transfusion in the analysis, (i.e. a Non-responder).
Time frame: Randomization (Visit 2), up to 7 Days following a scheduled procedure
Population: Full analysis Set (FAS) was defined as the group of all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg Placebo (Lower Baseline Platelet Count) | Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure | 34.9 Percentage of participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure | 68.6 Percentage of participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure | 33.3 Percentage of participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Percentage of Participants Who Did Not Require a Platelet Transfusion After Randomization and up to 7 Days Following a Scheduled Procedure | 87.9 Percentage of participants |
Comparison: The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the 60 mg avatrombopag and matched placebo treatment groups.p-value: =0.000695% CI: [15.8, 51.6]Cochran-Mantel-Haenszel
Comparison: The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the 60 mg avatrombopag and matched placebo treatment groups.p-value: <0.000195% CI: [36.5, 72.7]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Platelet Counts on Scheduled Procedure Day
Last observation carried forward was used for participants with a missing platelet count on the scheduled procedure day. Platelet count was measured preprocedure and before any platelet transfusion.
Time frame: Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)
Population: FAS. Only those participants with data available at both Baseline and post-Baseline were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg Placebo (Lower Baseline Platelet Count) | Change From Baseline in Platelet Counts on Scheduled Procedure Day | 3.0 platelet count x 10^9 per liter | Standard Deviation 10.01 |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Change From Baseline in Platelet Counts on Scheduled Procedure Day | 31.3 platelet count x 10^9 per liter | Standard Deviation 24.9 |
| 40 mg Placebo (Higher Baseline Platelet Count) | Change From Baseline in Platelet Counts on Scheduled Procedure Day | 5.9 platelet count x 10^9 per liter | Standard Deviation 14.89 |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Change From Baseline in Platelet Counts on Scheduled Procedure Day | 44.9 platelet count x 10^9 per liter | Standard Deviation 32.96 |
p-value: <0.000195% CI: [19.5, 32]Wilcoxon Rank Sum Test
p-value: <0.000195% CI: [25.5, 45.5]Wilcoxon Rank Sum Test
Secondary
Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day
Responders were defined as participants who achieved a platelet count greater than or equal to 50 x 10\^9/L on the procedure day. Participants missing a platelet count on the procedure day were conservatively considered as not achieving a platelet count of 50x10\^9/L in the analysis, (i.e. Non-responders).
Time frame: Day 10 to Day 13 (Visit 4)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg Placebo (Lower Baseline Platelet Count) | Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day | 7.0 Percentage of participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day | 67.1 Percentage of participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day | 39.4 Percentage of participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day | 93.1 Percentage of participants |
Comparison: The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the avatrombopag and placebo treatment groups.p-value: <0.000195% CI: [46.8, 73.5]Cochran-Mantel-Haenszel
Comparison: The null hypothesis was that the proportion of participants not requiring a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure was the same between the avatrombopag and placebo treatment groupsp-value: <0.000195% CI: [35.8, 71.6]Cochran-Mantel-Haenszel
Other Pre-specified
Number of Participants Experiencing an Adverse Event
Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious adverse events, including platelet transfusion-related complications; routine laboratory evaluation for hematology, serum chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); the performance of physical examinations; and Doppler sonography. AE severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Treatment-emergent adverse events (TEAEs) were defined as an AE that started on or after the date of first dose of study drug, up to 30 days after the last dose of study drug. Treatment-related AEs were considered by the investigator to be possibly or probably related to study drug.
Time frame: From date of first dose of study drug up to 30 days after the last dose of study drug, up to approximately 3 years and 2 months
Population: Safety analysis set included all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment. One participant in the High Baseline Platelet Count Cohort received 60 mg avatrombopag and hence was included in the \<40×10\^9/L Low Baseline Platelet Count Cohort in all safety analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose reduction | 0 Participants |
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose interruption | 0 Participants |
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Treatment-related TEAEs | 9 Participants |
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug withdrawal | 0 Participants |
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Serious TEAEs | 1 Participants |
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs | 22 Participants |
| 60 mg Placebo (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose adjustment | 0 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Treatment-related TEAEs | 6 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose adjustment | 0 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Serious TEAEs | 1 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs | 36 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose reduction | 0 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose interruption | 0 Participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug withdrawal | 0 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose interruption | 0 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose reduction | 0 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Treatment-related TEAEs | 2 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose adjustment | 0 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug withdrawal | 0 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs | 15 Participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Serious TEAEs | 1 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose interruption | 0 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose adjustment | 0 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs | 28 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Treatment-related TEAEs | 4 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | Serious TEAEs | 1 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug withdrawal | 0 Participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Number of Participants Experiencing an Adverse Event | TEAEs leading to study drug dose reduction | 0 Participants |
Other Pre-specified
Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure
The severity of bleeding events was assessed by the investigator (or appropriately delegated study site personnel) using the WHO bleeding scale. The WHO bleeding scale is a clinical investigator-assessed five-point scale with Grade 0 = No bleeding, Grade 1 = Petechial bleeding, Grade 2 = Mild blood loss (clinically significant), Grade 3 = Gross blood loss requires transfusion (severe), and Grade 4 = Debilitating blood loss, retinal or cerebral associated with fatality. Participants with missing information are considered as having a WHO bleeding score greater than or equal to 2 in the analysis.
Time frame: Baseline (Visit 2) up to 7 days post scheduled procedure
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 60 mg Placebo (Lower Baseline Platelet Count) | Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure | 0.0 Percentage of participants |
| 60 mg Avatrombopag (Lower Baseline Platelet Count) | Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure | 1.4 Percentage of participants |
| 40 mg Placebo (Higher Baseline Platelet Count) | Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure | 6.1 Percentage of participants |
| 40 mg Avatrombopag (Higher Baseline Platelet Count) | Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure | 1.7 Percentage of participants |