Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures

The study consists of 3 periods: a screening period (up to 28 days prior to randomization), a treatment period of 7 days (Days 1 to 7 during which study drug is to be administered for 4 to 7 days), and a posttreatment period (through 28 days posttreatment).

Once-daily treatment with lusutrombopag 3 mg or placebo is to commence on Day 1 and continue for up to 7 days. Platelet count is to be determined on Days 5, 6, and 7 prior to administration of study drug; if a participant meets the administration stopping criterion (ie, platelet count ≥ 50 × 10⁹/L with an increase of ≥ 20 × 10⁹/L from baseline), no additional dose of study drug is to be administered. The planned invasive procedure is to be performed in the posttreatment period between Days 9 and 14. Platelet count for determination of the need for platelet transfusion is to be determined on or after Day 8, but no more than 2 days prior to the invasive procedure; a platelet transfusion is required if the platelet count is < 50 × 10⁹/L.

Inclusion criteria

• Able to understand the study and comply with all study procedures.
• Willing to provide written informed consent prior to Screening.
• Male or female.
• 18 years of age or older at the time of signing informed consent.
• Platelet count < 50 × 10^9/L at baseline on Day 1 prior to randomization.
• Undergoing an elective invasive procedure.
• In the opinion of the investigator, able to meet study requirements.
• Male patients who are sterile or who agree to use an appropriate method of contraception (including use of a condom with spermicide) from Screening to completion of the Post-treatment Period.
• Female patients who are not postmenopausal or surgically sterile need to agree to use a highly effective contraception (including contraceptive implant, injectable contraceptive, combination hormonal contraceptive [including vaginal rings], intrauterine contraceptive device or vasectomised partner) from Screening to completion of the Post-treatment Period. Barrier method with or without spermicide, double barrier contraception and oral contraceptive pill are insufficient methods on their own.

Exclusion criteria

• Any of the following diseases:

• hematopoietic tumor
• aplastic anemia
• myelodysplastic syndrome
• myelofibrosis
• congenital thrombocytopenia
• drug-induced thrombocytopenia
• generalized infection requiring treatment except for viral liver disease
• immune thrombocytopenia.
• History of splenectomy.
• History of liver transplantation.
• Any of the following at Screening:

• hepatic encephalopathy uncontrolled by drugs
• ascites uncontrolled by drugs.
• Portal vein tumor embolism.
• Known to be positive for the human immunodeficiency virus.
• Past or present thrombosis or prothrombotic condition (e.g., cerebral infarction, myocardial infarction, angina pectoris, coronary artery stent placement, angioplasty, coronary artery bypass grafting, congestive heart failure [New York Heart Association Grade III/IV], arrhythmia known to increase the risk of thromboembolic events [atrial fibrillation], pulmonary thromboembolism, deep vein thrombosis, or disseminated intravascular coagulation syndrome).
• History or evidence of any of the following diseases:

• congenital thrombotic disease (eg, antithrombin deficiency, protein C deficiency, protein S deficiency, or coagulation factor [Factor V Leiden] mutation)
• acquired thrombotic disease (eg, antiphospholipid antibody syndrome, paroxysmal nocturnal hemoglobinuria, hyperhomocysteinemia, or increased factor VIII)
• Budd Chiari syndrome.
• Portal vein thrombosis based on ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) within 28 days prior to randomization or a history of portal vein thrombosis.
• Absence of hepatopetal blood flow in the main trunk of the portal vein as demonstrated by Doppler ultrasonography within 28 days prior to randomization.
• History or evidence of disease associated with a risk of bleeding (e.g., coagulation factor deficiency or von Willebrand factor deficiency).
• Bleeding score at randomization ≥ Grade 2 according to the World Health Organization (WHO) Bleeding Scale.
• Any of the following drugs or therapies within 90 days prior to randomization:

• anticancer drugs
• interferon preparations
• radiation therapy
• exsanguination
• other thrombopoietin receptor agonist
• any investigational agent.
• Any invasive procedure within 14 days prior to randomization.
• Blood transfusion within 14 days prior to randomization.
• Prior treatment with lusutrombopag (S-888711).
• Pregnancy or lactation.
• Known or suspected ongoing, active alcohol or substance abuse. Patients with a recent history who the investigator feels are able to comply with the study procedures and medications will be allowed to participate.
• Considered ineligible by the investigator for any other reason.