This is a phase 2, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag for Japanese subjects with thrombocytopenia associated with chronic liver disease. This study will assess the effect of avatrombopag on platelet counts in Japanese subjects. Subjects will be enrolled into 2 cohorts according to the mean platelet count measured at Screening and Baseline. Within the lower baseline platelet count cohort (less than 40 x 10^9/L), subjects will be randomized in a 1:1:1:3 ratio to receive placebo, 20 mg avatrombopag, 40 mg avatrombopag, or 60 mg avatrombopag for 5 days. Within the higher baseline platelet count cohort (from 40 to less than 50 x 10^9/L), subjects will be randomized in a 2:1:2 ratio to receive placebo, 20 mg avatrombopag, or 40 mg avatrombopag for 5 days.
Name: avatrombopag
Name: Placebo
Description: Responders were defined as participants whose platelet count was greater than or equal to 50×10^9/liter (L) and change from baseline was at least 20×10^9/L at Visit 4. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% confidence interval (CI) is calculated by Clopper and Pearson method.
Measure: Percentage of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L and at Least 20 x 10^9/L Increase From Baseline at Visit 4 Time: Baseline and Visit 4 (Day 10)Description: Responders were defined as the participants whose platelet count greater than or equal to 50 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% CI is calculated by Clopper and Pearson method.
Measure: Percentage of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Each Visit Time: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35)Description: Responders were defined as the participants whose platelet count greater than or equal to 75 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% CI is calculated by Clopper and Pearson method.
Measure: Percentage of Participants With Platelet Count Greater Than or Equal to 75 x 10^9/L at Each Visit Time: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35)Description: Responders were defined as the participants whose platelet count greater than or equal to 150 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis.
Measure: Percentage of Participants With Platelet Count Greater Than or Equal to 150 x 10^9/L At Each Visit Time: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35)Description: Responders were defined as the participants whose platelet count greater than or equal to 200 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis.
Measure: Percentage of Participants With Platelet Count Greater Than or Equal to 200 x 10^9/L At Each Visit Time: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35)Description: Safety assessments consisted of monitoring and recording all AEs and SAEs, regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms; 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. A treatment-emergent adverse event (TEAE) was 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. For each category, a participant with two or more adverse events in that category was counted only once. Treatment-related TEAEs were considered by the investigator to be possibly or probably related to study drug or TEAEs with a missing causality.
Measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Time: From the date of first dose of study drug up to 30 days after the last dose of the study drug, up to approximately 10 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency etc.) 17. --- G20210A ---