Clinical trial NCT00914927: Once-Daily Oral Avatrombopag Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures
Official title: A Phase 2, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study to Evaluate the Efficacy, Safety, and Population Pharmacokinetics of Once-Daily Oral E5501 Tablets Used Up to 7 Days in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thrombocytopenia Related to Chronic Liver Disease
Keywords: Thrombocytopenia
chronic liver disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2009-06-05
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Response
timeFrame: Day 8 (Visit 5, EOT)
Secondary outcomes:
measure: Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline
timeFrame: Day 8 (Visit 5, EOT)
measure: Percentage of Participants Experiencing Dose-response by Visit
timeFrame: Day 4 (Visit 3), Day 6 ( Visit 4), Day 8 (Visit 5, EOT), 3 Day Post Last Dose (Visit 6), and 7 Day Post Last Dose (Visit 7)
measure: Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4
timeFrame: Day 4 (Visit 3)
measure: Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8
timeFrame: Day 4 (Visit 3) and Day 8 (Visit 5, EOT)
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
Study officials:
affiliation: Eisai Inc.
name: Tim Jenkins
role: STUDY_DIRECTOR
References: