Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing an Elective Procedure

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.

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 109/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 109/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. Adequate portal vein blood flow 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