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

Phase 2

Completed

• Conditions: Thrombocytopenia Related to Chronic Liver Disease
• Interventions: Drug: Avatrombopag; Drug: Placebo

• Registration Number: NCT00914927
• Lead Sponsor: Eisai Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05
• Study First Submitted: 2009-06-04
• Study First Submitted QC: 2009-06-04
• Study First Posted: 2009-06-05
• Primary Completion: 2011-11-11
• Study Completion: 2011-12-21
• Disposition First Submitted: 2013-05-21
• Disposition First Submitted QC: 2013-05-21
• Disposition First Posted: 2013-05-29
• Results First Submitted: 2017-12-05
• Status Verified: 2018-01
• Results First Submitted QC: 2018-01-19
• Last Update Submitted: 2018-01-19
• Results First Posted: 2018-01-23
• Last Update Posted: 2018-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Avatrombopag	-
2	Avatrombopag	-
2	Placebo	-
3	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Response	Day 8 (Visit 5, EOT)	Platelet counts (PC) were determined from blood draws. A responder is defined as a participant having an increase of at least 20,000/mm\^3 PC from Baseline and a PC greater than 50,000/mm\^3 at least once during Day 4 through Day 8. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (end of treatment (EOT)), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.

Secondary Outcome Measures

Name	Time	Method
Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline	Day 8 (Visit 5, EOT)	Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Percentage of Participants Experiencing Dose-response by Visit	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)	Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4	Day 4 (Visit 3)	Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.
Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8	Day 4 (Visit 3) and Day 8 (Visit 5, EOT)	Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used.

Trial Locations

Locations (1)

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States