Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
Condition: Chronic Liver Disease; Thrombocytopenia
MeSH terms: Liver Diseases; Thrombocytopenia
Intervention: Lusutrombopag; Placebo
Intervention description: Tablets for oral administration; Tablets for oral administration
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Elective invasive procedures

Summary:

      The primary purpose of this study is to compare the efficacy of lusutrombopag with placebo
      for the treatment of thrombocytopenia in patients with chronic liver disease who are
      undergoing elective invasive procedures.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to understand the study and comply with all study procedures.

          2. Willing to provide written informed consent prior to Screening.

          3. Male or female.

          4. 18 years of age or older at the time of signing informed consent.

          5. Platelet count < 50 × 10^9/L at baseline on Day 1 prior to randomization.

          6. Undergoing an elective invasive procedure.

          7. In the opinion of the investigator, able to meet study requirements.

          8. 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.

          9. 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:

          1. 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.

          2. History of splenectomy.

          3. History of liver transplantation.

          4. Any of the following at Screening:

               -  hepatic encephalopathy uncontrolled by drugs

               -  ascites uncontrolled by drugs.

          5. Portal vein tumor embolism.

          6. Known to be positive for the human immunodeficiency virus.

          7. 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).

          8. 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.

          9. 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.

         10. Absence of hepatopetal blood flow in the main trunk of the portal vein as demonstrated
             by Doppler ultrasonography within 28 days prior to randomization.

         11. History or evidence of disease associated with a risk of bleeding (e.g., coagulation
             factor deficiency or von Willebrand factor deficiency).

         12. Bleeding score at randomization ≥ Grade 2 according to the World Health Organization
             (WHO) Bleeding Scale.

         13. 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.

         14. Any invasive procedure within 14 days prior to randomization.

         15. Blood transfusion within 14 days prior to randomization.

         16. Prior treatment with lusutrombopag (S-888711).

         17. Pregnancy or lactation.

         18. 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.

         19. Considered ineligible by the investigator for any other reason.