Thrombocytopenia Related to Chronic Liver Disease
Conditions
Keywords
Thrombocytopenia, chronic liver disease
Brief summary
The purpose of this study is to evaluate the efficacy of once-daily Oral avatrombopagin subjects with chronic liver diseases and thrombocytopenia prior to elective surgical or diagnostic procedures, to evaluate the safety of short-term administration of avatrombopag and to evaluate the pharmacokinetics (PK) of E5501.
Interventions
DRUGAvatrombopag
Avatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days
DRUGPlacebo
Placebo or inactive substance once a day for up to 7 days
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Males or females ≥ 18 years of age 2. Thrombocytopenia (defined as a platelet count ≥ 10,000 - ≤ 50,000 (+15%)/mm\^3 ) 3. Model for End-Stage Liver Disease (MELD) scores ≤ 24 4. Chronic liver diseases due to one of the following three etiologies: Chronic Viral Hepatitis from one of the following categories * Chronic Hepatitis C (defined as the presence of anti-hepatitis C virus \[HCV\] antibodies and/or detectable serum HCV ribonucleic acid \[RNA\] levels) * OR chronic Hepatitis B (defined as the presence of hepatitis B surface antigen \[HBsAg\] and/or detectable serum hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\]) * OR chronic Hepatitis B and C co-infection (as defined by the above bullet points) * OR chronic Hepatitis C and history of alcohol abuse * OR chronic Hepatitis B and history of alcohol abuse NASH diagnosed as: * absence of serologic evidence of viral hepatitis and * convincing evidence of a history of minimal or no alcohol consumption, and * histologic picture of steatohepatitis OR * when histology is unavailable, then clinical, radiographic and laboratory evidence of NASH Alcoholic liver disease diagnosed as: * absence of serologic evidence of viral hepatitis and * history of heavy alcohol consumption and * histologic picture of alcoholic liver disease OR * when histology is unavailable, then clinical, radiographic and laboratory evidence of hepatitis combined with years of excessive alcohol intake 5. Subjects who are scheduled to undergo an elective invasive procedure between 1 to 4 days post last dose of study drug. 6. Adequate renal function as evidenced by a calculated creatinine clearance ≥50 mL/minute per the Cockcroft and Gault formula 7. Life expectancy ≥3 months Key
Exclusion criteria
1. Hepatic encephalopathy that cannot be effectively treated. 2. Platelet transfusion within 7 days prior to the first dose of study drug 3. Received blood products, eg, FFP and cryoprecipitate 7 days prior to the first dose of study drug 4. Have surgical or diagnostic procedure scheduled during the Randomization Phase (Day 1 to Day 8) of this study 5. Interferon use within 2 weeks of Day 1 6. Hormonal contraceptive use within 60 days of study entry 7. History of human immunodeficiency virus (HIV) infection 8. Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1 9. Active alcohol abuse, active alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) 10. Acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start 11. History of any primary hematologic disorder 12. History of arterial or venous thrombosis, including thrombosis of any part of the splenic-mesenteric system 13. Any evidence of current portal vein thrombosis (PVT) as detected by Doppler sonography or appropriate MRI/CT imaging at Screening and/or within approximately 30 days prior to Screening 14. Any acute/active bleeding (gastrointestinal \[GI\], central nervous system \[CNS\], etc) 15. Uncompensated congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) 16. Pre-diagnosed Immune Thrombocytopenic Purpura (ITP) 17. History of Myelodysplastic Syndrome (MDS) 18. Females who are pregnant (positive β-hCG test ) or breastfeeding 19. Current use of recreational drugs 20. Post-transplant patients 21. Subjects who have participated in another investigational trial within 30 days prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Response | Day 8 (Visit 5, EOT) | Platelet counts (PC) were determined from blood draws. A responder is defined as a participant having an increase of at least 20,000/mm\^3 PC from Baseline and a PC greater than 50,000/mm\^3 at least once during Day 4 through Day 8. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (end of treatment (EOT)), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | Day 8 (Visit 5, EOT) | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. |
| Percentage of Participants Experiencing Dose-response by Visit | Day 4 (Visit 3), Day 6 ( Visit 4), Day 8 (Visit 5, EOT), 3 Day Post Last Dose (Visit 6), and 7 Day Post Last Dose (Visit 7) | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. |
| Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Day 4 (Visit 3) | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. |
| Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Day 4 (Visit 3) and Day 8 (Visit 5, EOT) | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: 20 mg Avatrombopag, 1G Formulation Participants received a 100 mg loading dose of the first generation (1G) formulation avatrombopag on Day 1, followed by 20 mg of the 1G formulation avatrombopag once daily on Days 2 to 7. | 18 |
| Cohort A: 40 mg Avatrombopag, 1G Formulation Participants received a 100 mg loading dose of the 1G formulation avatrombopag on Day 1, followed by 40 mg of the 1G formulation avatrombopag once daily on Days 2 to 7. | 16 |
| Cohort A: 80 mg Avatrombopag, 1G Formulation Participants received a 100 mg loading dose of the 1G formulation avatrombopag on Day 1, followed by 80 mg of the 1G formulation avatrombopag once daily on Days 2 to 7. | 17 |
| Cohort A: Placebo, 1G Formulation Participants received the 1G formulation avatrombopag-matched placebo loading dose on Day 1, then once daily on Days 2 to 7. | 16 |
| Cohort B: 10 mg Avatrombopag, 2G Formulation Participants received an 80 mg loading dose of the second generation (2G) formulation avatrombopag on Day 1, followed by 10 mg 2G formulation avatrombopag once daily on Days 2 to 7. | 21 |
| Cohort B: 20 mg Avatrombopag, 2G Formulation Participants received an 80 mg loading dose of the 2G formulation avatrombopag on Day 1, followed by 20 mg 2G formulation avatrombopag once daily on Days 2 to 4 followed by 2G avatrombopag-matched placebo once daily on Days 5 to 7. | 21 |
| Cohort B: Placebo, 2G Formulation Participants received the 2G formulation avatrombopag-matched placebo loading dose on Day 1, then once daily on Days 2 to 7. | 21 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative/Other | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A: 20 mg Avatrombopag, 1G Formulation | Cohort A: 40 mg Avatrombopag, 1G Formulation | Cohort A: 80 mg Avatrombopag, 1G Formulation | Cohort A: Placebo, 1G Formulation | Cohort B: 10 mg Avatrombopag, 2G Formulation | Cohort B: 20 mg Avatrombopag, 2G Formulation | Cohort B: Placebo, 2G Formulation | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 7.16 | 52.8 Years STANDARD_DEVIATION 7.78 | 55.2 Years STANDARD_DEVIATION 5.96 | 54.2 Years STANDARD_DEVIATION 6.87 | 53.9 Years STANDARD_DEVIATION 5.48 | 56.8 Years STANDARD_DEVIATION 6.46 | 55.6 Years STANDARD_DEVIATION 6.52 | 54.8 Years STANDARD_DEVIATION 6.56 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 6 Participants | 5 Participants | 10 Participants | 7 Participants | 7 Participants | 42 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 11 Participants | 11 Participants | 11 Participants | 14 Participants | 14 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 16 | 0 / 17 | 0 / 16 | 1 / 21 | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 17 / 18 | 13 / 16 | 13 / 17 | 12 / 16 | 17 / 21 | 18 / 21 | 16 / 21 |
| serious Total, serious adverse events | 3 / 18 | 2 / 16 | 3 / 17 | 1 / 16 | 5 / 21 | 3 / 21 | 3 / 21 |
Outcome results
Primary
Percentage of Participants Experiencing Response
Platelet counts (PC) were determined from blood draws. A responder is defined as a participant having an increase of at least 20,000/mm\^3 PC from Baseline and a PC greater than 50,000/mm\^3 at least once during Day 4 through Day 8. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (end of treatment (EOT)), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Time frame: Day 8 (Visit 5, EOT)
Population: Intent-to-treat (ITT) population included all participants who were randomized into the study, received study medication, and had a posttreatment assessment. The ITT population was analyzed as randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Response | Yes response | 38.9 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Response | No response | 61.1 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Response | Yes response | 31.3 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Response | No response | 68.8 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Response | Yes response | 76.5 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Response | No response | 23.5 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Response | Yes response | 6.3 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Response | No response | 93.8 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Response | Yes response | 42.9 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Response | No response | 57.1 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Response | Yes response | 52.4 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Response | No response | 47.6 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Response | Yes response | 9.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Response | No response | 90.5 Percentage of participants |
Secondary
Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline
Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Time frame: Day 8 (Visit 5, EOT)
Population: Intent-to-treat population included all participants who were randomized into the study, received study medication, and had a posttreatment assessment. The ITT population was analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 16.2 K/mm^3 | Standard Deviation 10.32 |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 15.9 K/mm^3 | Standard Deviation 13.45 |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 32.2 K/mm^3 | Standard Deviation 18.59 |
| Cohort A: Placebo, 1G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 3.1 K/mm^3 | Standard Deviation 17.97 |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 18.9 K/mm^3 | Standard Deviation 10.07 |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 24.9 K/mm^3 | Standard Deviation 17.91 |
| Cohort B: Placebo, 2G Formulation | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | 3.9 K/mm^3 | Standard Deviation 12.49 |
Secondary
Percentage of Participants Experiencing Dose-response by Visit
Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Time frame: Day 4 (Visit 3), Day 6 ( Visit 4), Day 8 (Visit 5, EOT), 3 Day Post Last Dose (Visit 6), and 7 Day Post Last Dose (Visit 7)
Population: Intent-to-treat population included all participants who were randomized into the study, received study medication, and had a posttreatment assessment. The ITT population was analyzed as randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 11.1 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 61.1 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 38.9 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 44.4 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 55.6 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 38.9 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 61.1 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 88.9 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 37.5 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 62.5 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 12.5 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 31.3 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 68.8 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 87.5 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 43.8 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 56.3 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 82.4 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 88.2 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 5.9 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 94.1 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 29.4 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 70.6 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 76.5 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 23.5 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 17.6 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 11.8 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 12.5 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 6.3 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 93.8 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 87.5 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 100.0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 87.5 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 12.5 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 85.7 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 57.1 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 71.4 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 14.3 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 28.6 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 33.3 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 42.9 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 66.7 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 47.6 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 95.2 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 52.4 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 61.9 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 33.3 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 66.7 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 4.8 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 61.9 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 38.1 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 38.1 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 6, Visit 4) | 9.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (7 Day post last dose, Visit 7) | 90.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 6, Visit 4) | 90.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 8, Visit 5) | 9.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 8, Visit 5) | 90.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (3 Day post last dose, Visit 6) | 9.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (3 Day post last dose, Visit 6) | 90.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (7 Day post last dose, Visit 7) | 9.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | No response (Day 4, Visit 3) | 95.2 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Experiencing Dose-response by Visit | Yes response (Day 4, Visit 3) | 4.8 Percentage of participants |
Secondary
Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8
Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Time frame: Day 4 (Visit 3) and Day 8 (Visit 5, EOT)
Population: Intent-to-treat population included all participants who were randomized into the study, received study medication, and had a posttreatment assessment. The ITT population was analyzed as randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 94.4 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 5.6 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 94.4 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 5.6 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 0 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 100.0 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 11.8 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 88.2 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 100.0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 95.2 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 4.8 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 90.5 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 9.5 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 8, Visit 5) | 0 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 8, Visit 5) | 100.0 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Yes response (Day 4, Visit 3) | 0 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | No response (Day 4, Visit 3) | 100.0 Percentage of participants |
Secondary
Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4
Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Time frame: Day 4 (Visit 3)
Population: Intent-to-treat population included all participants who were randomized into the study, received study medication, and had a posttreatment assessment. The ITT population was analyzed as randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 94.4 Percentage of participants |
| Cohort A: 20 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 5.6 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 0 Percentage of participants |
| Cohort A: 40 mg Avatrombopag , 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 100.0 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 100.0 Percentage of participants |
| Cohort A: 80 mg Avatrombopag, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 0 Percentage of participants |
| Cohort A: Placebo, 1G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 100.0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 0 Percentage of participants |
| Cohort B:10 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 100.0 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 0 Percentage of participants |
| Cohort B: 20 mg Avatrombopag, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 100.0 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | No response | 100.0 Percentage of participants |
| Cohort B: Placebo, 2G Formulation | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Yes response | 0 Percentage of participants |