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

NCT00914927 | Completed Phase 2 Results

• 1 other identifier: E5501-G000-202
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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

Keywords

Thrombocytopenia; chronic liver disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Experiencing Response

  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.

  Day 8 (Visit 5, EOT)

Secondary Outcomes (4)

• Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline

  Day 8 (Visit 5, EOT)

• 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)

• Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4

  Day 4 (Visit 3)

• 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)

Study Arms (3)

1

EXPERIMENTAL

Drug: Avatrombopag

2

EXPERIMENTAL

Drug: Avatrombopag; Drug: Placebo

3

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Avatrombopag DRUG

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

1

Placebo DRUG

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

2; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females ≥ 18 years of age
• Thrombocytopenia (defined as a platelet count ≥ 10,000 - ≤ 50,000 (+15%)/mm\^3 )
• Model for End-Stage Liver Disease (MELD) scores ≤ 24
• 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

You may not qualify if:

• Hepatic encephalopathy that cannot be effectively treated.
• Platelet transfusion within 7 days prior to the first dose of study drug
• Received blood products, eg, FFP and cryoprecipitate 7 days prior to the first dose of study drug
• Have surgical or diagnostic procedure scheduled during the Randomization Phase (Day 1 to Day 8) of this study
• Interferon use within 2 weeks of Day 1
• Hormonal contraceptive use within 60 days of study entry
• History of human immunodeficiency virus (HIV) infection
• Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1
• 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)
• Acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start
• History of any primary hematologic disorder
• History of arterial or venous thrombosis, including thrombosis of any part of the splenic-mesenteric system
• 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
• Any acute/active bleeding (gastrointestinal \[GI\], central nervous system \[CNS\], etc)
• Uncompensated congestive heart failure (New York Heart Association \[NYHA\] Class III or IV)

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

MeSH Terms

Conditions

Thrombocytopenia

Interventions

avatrombopag

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai Inc.

1-888-422-4743

Study Officials

• Tim Jenkins

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2009
• First Posted: June 5, 2009
• Study Start: May 1, 2009
• Primary Completion: November 11, 2011
• Study Completion: December 21, 2011
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2018

Record last verified: 2018-01

Locations

US (1)