Clinical Trials

Inclusion Criteria

• ≥ 18 years of age at screening
• Have chronic liver disease
• Have a mean baseline platelet count of < 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 > 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
• Scheduled to undergo a permitted elective procedure and 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 change in platelet count from baseline
• Model For End-stage Liver Disease (MELD) score ≤ 24 at screening
• If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to screening
• Provide written informed consent
• Willing and able to comply with all aspects of the protocol

Exclusion Criteria

• Any history of arterial or venous thrombosis, including partial or complete thrombosis
• Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at screening
• Adequate portal vein blood flow at screening
• Hepatic encephalopathy that cannot be effectively treated
• Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D
• Platelet transfusion or receipt of blood products containing platelets within 7 days of screening
  • Packed red blood cells are permitted
• Within 7 days of screening no
  • Heparin
  • Warfarin
  • Nonsteroidal anti-inflammatory drugs (NSAID)
  • Aspirin
  • Verapamil
  • Antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban)
• Use of erythropoietin stimulating agents within 7 days of screening
• Interferon (IFN) use within 14 days of screening
• Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of screening
• Active infection requiring systemic antibiotic therapy within 7 days of screening
  • Prophylactic use of antibiotics is permitted
• Within 6 months of the study start (unless participating in a controlled rehabilitation program), no
  • Alcohol abuse
  • Alcohol dependence syndrome
  • Drug abuse
  • Drug dependence  
• Acute alcoholic hepatitis within 6 months of the study start (chronic alcoholic hepatitis is allowed)
• Elective procedure performed prior to visit 4 (Procedure Day)
• Known to be human immunodeficiency virus positive
• Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system)
• Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome)
• Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency etc.)
• 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)
• Females of childbearing potential who have had unprotected sexual intercourse within 30 days before study entry 
• Females of childbearing potential who do not agree to use a highly effective method of contraception throughout the entire study period and for 30 days after study drug discontinuation eg
  • Total abstinence
    • Must agree to use a double-barrier method if she becomes sexually active during the study period or for 30 days after study drug discontinuation
  • An intrauterine device
  • A double-barrier method such as condom plus diaphragm with spermicide
  • A progesterone-only contraceptive implant/injection
  • Have a vasectomized partner with confirmed azoospermia  
  • 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) 
    • Have been sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing
• 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
• Post liver transplant subjects
• Has previously received avatrombopag
• Hypersensitivity to avatrombopag maleate or any of its excipients
• 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
• Current malignancy including solid tumors and hematologic malignancies (except HCC)
• 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
• Currently enrolled in another clinical trial with any investigational drug or device within 30 days of screening