Ensayos clínicos

Inclusion Criteria:

• Subject is ≥18 years of age at the time of informed consent.
• Subject has a mean baseline platelet count between:
  • 50 × 109/L and <100 × 109/L in subjects without a diagnosis of chronic liver disease;
  • OR
  • 50 × 109/L and <75 × 109/L in subjects with diagnosed chronic liver disease.
• Platelet counts must be measured on 2 separate occasions, and must be performed at least 1 day apart with neither platelet count ≥100 × 109/L in subjects without CLD and ≥75 × 109/L in subjects with CLD. One standard of care platelet count measurement may be used if collected within 14 days of Baseline and the mean of these 2 platelet counts (mean baseline platelet count) will be used for entry criteria.
  • Subject is scheduled to undergo operations to critical sites (e.g., eye surgery, neurosurgery) or operations with a high risk of bleeding (e.g., major abdominal surgery);
  • OR
  • In the opinion of the Investigator, would otherwise require a pre-operative platelet transfusion to prevent bleeding.
• Female subjects of childbearing potential must 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]; hormonal contraceptive given orally, by injection, or by implant; or has 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.
  • Note: All female subjects are considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group and without another known or suspected cause) or has been sterilized surgically (e.g., bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing.
  • Subject is willing and able to comply with all aspects of the protocol;
  • AND
  • Subject (or legally authorized representative) must provide written informed consent.

Exclusion Criteria

• Subject has a history of arterial or venous thrombosis within the previous 6 months of Baseline.
• Known portal vein blood flow velocity rate <10 cm/second or previous occurrence of a portal vein thrombosis within 6 months of Baseline.
• Subject plans to have a platelet transfusion or plans to receive blood products containing platelets within 7 days of the Baseline Visit; however, packed red blood cells are permitted.
• Subject is unable to temporarily withhold anticoagulant or antiplatelet therapy per local standard of care prior to the operation (low dose aspirin may be continued).
• Use of erythropoietin-stimulating agents within 7 days of the Baseline Visit.
• Use of moderate or strong inducers of cytochrome P450 (CYP) 2C9 or CYP3A4/5 from 7 days prior to Baseline through the end of the dosing regimen.
• Current use of a thrombopoietin receptor agonist (e.g., eltrombopag or romiplostim).
• Subject has an active infection requiring systemic antibiotic therapy within 7 days of the Baseline Visit; however, prophylactic use of antibiotics is permitted.
• Subject with alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the Baseline Visit (unless participating in a controlled rehabilitation program) or alcoholic hepatitis within 6 months of the Screening Visit.
• Subject has a surgery between the Baseline Visit and Visit 4 (Procedure Day).
• Subject is known to be human immunodeficiency virus positive.
• Subject has any clinically significant bleeding at the Baseline Visit.
• Subject has a known medical history of genetic prothrombotic syndromes (e.g., Factor V Leiden, prothrombin G20210A, ATIII deficiency, etc.).
• Subject has a recent history (within the previous 6 months) of significant cardiovascular disease (e.g., exacerbation of congestive heart failure, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary or peripheral artery stent placement or angioplasty, and coronary or peripheral artery bypass graft).
• Female subjects who are lactating or pregnant at the Baseline Visit (as documented by a positive serum beta-human chorionic gonadotropin [β-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG) or are planning to become pregnant during the study.
• Subject has a hypersensitivity to avatrombopag or any of its excipients.
• Subject has hemoglobin levels ≤8.0 g/dL or ≥18.0 g/dL for males and >15 g/dL for females at the Baseline Visit, with hematocrit ≥54% for males and ≥45% for females.
• Subject has prothrombin time/international normalized ratio and activated partial thromboplastin time outside 80% to 120% of the normal range.
• Subject with a current malignancy including solid tumors and hematologic malignancies whose thrombocytopenia may be attributed to chemotherapy.
• Hepatic encephalopathy that cannot be effectively treated.
• Subjects with hepatocellular carcinoma (HCC) and Barcelona Clinic Liver Cancer (BCLC) staging classification C or D.
  • Subject has any history of a concomitant medical condition that, in the opinion of the Investigator, would compromise the subject’s ability to safely complete the study;
  • OR
  • Subject is currently enrolled in another clinical study with any investigational drug or device within 30 days of the Baseline Visit; however, participation in observational studies is permitted.