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.

This study will consist of Prerandomization Phase and Randomization Phase. The Prerandomization Phase includes a Screening Period (Day -28 to Day -1) and a Baseline Period (Day 1). During the Prerandomization Phase, participants will be divided into two cohorts based on the platelet count: Low Platelet Count Cohort and High Platelet Count Cohort. Participants in Low Platelet Count Cohort will be randomized to receive one of the four treatments: Placebo, Avatrombopag 20 mg, Avatrombopag 40 mg, or Avatrombopag 60 mg. Participants in High Platelet Count Cohort will be randomized to receive one of the three treatments: Placebo, Avatrombopag 20 mg, or Avatrombopag 40 mg.

The Randomization Phase includes the Treatment Period and the Follow-up Period. The Follow-up Period comprises 3 visits: Visit 4 (5 to 8 days after last dose of study drug [Study Day 10 to 13]), Visit 5 (12 to 15 days after last dose of study drug [Study Day 17 to 20]), and 30 days after receiving the last dose of study drug.

Inclusion Criteria

1. Japanese subjects greater than or equal to 20 years of age at Screening with chronic liver disease.
2. Subjects who have a mean baseline platelet count of less than 50 x 10^9/L. Platelet counts will 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.
3. Model For End-stage Liver Disease (MELD) score 24 at Screening.
4. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening.
5. Provide written informed consent.
6. 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 less than 10 cm/second at Screening.
4. Hepatic encephalopathy that cannot be effectively treated.
5. Subjects 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. Known to be human immunodeficiency virus positive.
14. Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system).
15. Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome).
16. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency etc.)
17. Subjects 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).
18. 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 subject 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.
19. 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.
20. Post liver transplant subjects.
21. Any subject who has previously received avatrombopag.
22. Hypersensitivity to avatrombopag maleate or any of its excipients.
23. Hemoglobin levels less than or equal to 8.0 or greater than or equal to 16.0 g/dL at Screening.
24. White blood cell count less than or equal to 1.5 x 10^9/L or greater than or equal to 15.0 x 10^9/L at Screening.
25. Serum sodium level less than or equal to 130 milliequivalents/L at Screening.
26. Current malignancy including solid tumors and hematologic malignancies (except HCC).
27. Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator(s), would compromise the subject's ability to safely complete the study.
28. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days of Screening.