Once-Daily Oral Avatrombopag Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures
Condition: Thrombocytopenia Related to Chronic Liver Disease
MeSH terms: Liver Diseases; Thrombocytopenia
Intervention: Avatrombopag; Avatrombopag; Placebo
Intervention description: Avatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days; Avatrombopag first Dose 80 mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days; Placebo or inactive substance once a day for up to 7 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 130.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Thrombocytopenia; chronic liver disease

Summary:

      The purpose of this study is to evaluate the efficacy of once-daily Oral avatrombopagin
      subjects with chronic liver diseases and thrombocytopenia prior to elective surgical or
      diagnostic procedures, to evaluate the safety of short-term administration of avatrombopag
      and to evaluate the pharmacokinetics (PK) of E5501.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Males or females ≥ 18 years of age

          2. Thrombocytopenia (defined as a platelet count ≥ 10,000 - ≤ 50,000 (+15%)/mm^3 )

          3. Model for End-Stage Liver Disease (MELD) scores ≤ 24

          4. Chronic liver diseases due to one of the following three etiologies:

             Chronic Viral Hepatitis from one of the following categories

               -  Chronic Hepatitis C (defined as the presence of anti-hepatitis C virus [HCV]
                  antibodies and/or detectable serum HCV ribonucleic acid [RNA] levels)

               -  OR chronic Hepatitis B (defined as the presence of hepatitis B surface antigen
                  [HBsAg] and/or detectable serum hepatitis B virus [HBV] deoxyribonucleic acid
                  [DNA])

               -  OR chronic Hepatitis B and C co-infection (as defined by the above bullet points)

               -  OR chronic Hepatitis C and history of alcohol abuse

               -  OR chronic Hepatitis B and history of alcohol abuse

             NASH diagnosed as:

               -  absence of serologic evidence of viral hepatitis and

               -  convincing evidence of a history of minimal or no alcohol consumption, and

               -  histologic picture of steatohepatitis OR

               -  when histology is unavailable, then clinical, radiographic and laboratory
                  evidence of NASH

             Alcoholic liver disease diagnosed as:

               -  absence of serologic evidence of viral hepatitis and

               -  history of heavy alcohol consumption and

               -  histologic picture of alcoholic liver disease OR

               -  when histology is unavailable, then clinical, radiographic and laboratory
                  evidence of hepatitis combined with years of excessive alcohol intake

          5. Subjects who are scheduled to undergo an elective invasive procedure between 1 to 4
             days post last dose of study drug.

          6. Adequate renal function as evidenced by a calculated creatinine clearance ≥50
             mL/minute per the Cockcroft and Gault formula

          7. Life expectancy ≥3 months

        Key Exclusion Criteria:

          1. Hepatic encephalopathy that cannot be effectively treated.

          2. Platelet transfusion within 7 days prior to the first dose of study drug

          3. Received blood products, eg, FFP and cryoprecipitate 7 days prior to the first dose of
             study drug

          4. Have surgical or diagnostic procedure scheduled during the Randomization Phase (Day 1
             to Day 8) of this study

          5. Interferon use within 2 weeks of Day 1

          6. Hormonal contraceptive use within 60 days of study entry

          7. History of human immunodeficiency virus (HIV) infection

          8. Any prohibited concomitant medications or therapy that cannot be discontinued by Visit
             1

          9. Active alcohol abuse, active alcohol dependence syndrome, drug abuse, or drug
             dependence within 6 months of the study start (unless participating in a controlled
             rehabilitation program)

         10. Acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of
             the study start

         11. History of any primary hematologic disorder

         12. History of arterial or venous thrombosis, including thrombosis of any part of the
             splenic-mesenteric system

         13. Any evidence of current portal vein thrombosis (PVT) as detected by Doppler sonography
             or appropriate MRI/CT imaging at Screening and/or within approximately 30 days prior
             to Screening

         14. Any acute/active bleeding (gastrointestinal [GI], central nervous system [CNS], etc)

         15. Uncompensated congestive heart failure (New York Heart Association [NYHA] Class III or
             IV)

         16. Pre-diagnosed Immune Thrombocytopenic Purpura (ITP)

         17. History of Myelodysplastic Syndrome (MDS)

         18. Females who are pregnant (positive β-hCG test ) or breastfeeding

         19. Current use of recreational drugs

         20. Post-transplant patients

         21. Subjects who have participated in another investigational trial within 30 days prior
             to Visit 1.