Once-Daily Oral Avatrombopag Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures

NCT ID: NCT00914927

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2011-12-21

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.

Conditions

Thrombocytopenia Related to Chronic Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

Avatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days

2

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

Avatrombopag first Dose 80 mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days

Placebo

Intervention Type: DRUG

Placebo or inactive substance once a day for up to 7 days

3

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo or inactive substance once a day for up to 7 days

Interventions

Avatrombopag

Avatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days

Intervention Type: DRUG

Avatrombopag

Avatrombopag first Dose 80 mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days

Intervention Type: DRUG

Placebo

Placebo or inactive substance once a day for up to 7 days

Intervention Type: DRUG

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Jenkins

Role: STUDY_DIRECTOR

Eisai Inc.

Locations

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Countries

United States

Other Identifiers

E5501-G000-202

Identifier Type: -

Identifier Source: org_study_id