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

Protocol: 
E5501-G000-311
Phase: 
III

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

A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults with Thrombocytopenia Associated with Liver Disease Prior to an Elective Procedure

This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag to treat adults with thrombocytopenia associated with liver disease. The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with liver disease prior to an elective procedure to reduce the need for platelet transfusions or any rescue procedure for bleeding due to procedural and post-procedural bleeding complications. Subjects will be enrolled into 2 cohorts according to mean baseline platelet count and, within each baseline platelet count cohort will be further stratified by risk of bleeding associated with the elective procedure (low, moderate, or high) and hepatocellular carcinoma (HCC) status (Yes or No).

Are you Eligible? (Inclusion Criteria)

Inclusion Criteria

  • Subjects greater than or equal to 18 years of age at Screening with chronic liver disease
  • Subjects who have a mean baseline platelet count of less than 50 x 10^9/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 10^9/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.
  • Subjects 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
  • Model For End-stage Liver Disease (MELD) score less than or equal to 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
  • Subjects 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. However packed red blood cells are permitted.
  • 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
  • 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. However, prophylactic use of antibiotics is permitted.
  • 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
  • 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
  • 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)
  • 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.
  • 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
  • Any subject who has previously received avatrombopag
  • Hypersensitivity to avatrombopag maleate or any of its excipients
  • Hemoglobin levels less than or equal to 8.0 or greater than or equal to 16.0 g/dL at Screening
  • 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
  • Serum sodium level less than or equal to 130 mEq/L at Screening
  • Current malignancy including solid tumors and hematologic malignancies (except HCC)
  • Any history of or concomitant medical condition that, in the opinion of the investigator(s), would compromise the subject's ability to safely complete the study
  • Currently enrolled in another clinical trial or used any investigational drug or device within 30 days of Screening

Specialty Area(s)

Trial Location

NYP/Columbia
New York, NY 10032
United States