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

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ClinicalTrials.gov Identifier: NCT00914927
Recruitment Status : Completed
First Posted : June 5, 2009
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Thrombocytopenia Related to Chronic Liver Disease Drug: Avatrombopag Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : May 2009
Primary Completion Date : November 11, 2011
Study Completion Date : December 21, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1 Drug: Avatrombopag
Avatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days
Experimental: 2 Drug: Avatrombopag
Avatrombopag first Dose 80 mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days
Drug: Placebo
Placebo or inactive substance once a day for up to 7 days
Placebo Comparator: 3 Drug: Placebo
Placebo or inactive substance once a day for up to 7 days



Primary Outcome Measures :
  1. Percentage of Participants Experiencing Response [ Time Frame: 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 :
  1. Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline [ Time Frame: 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.

  2. Percentage of Participants Experiencing Dose-response by Visit [ Time Frame: 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.

  3. Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 [ Time Frame: 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.

  4. Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00914927


Locations
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Tim Jenkins Eisai Inc.

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00914927     History of Changes
Other Study ID Numbers: E5501-G000-202
First Posted: June 5, 2009    Key Record Dates
Results First Posted: January 23, 2018
Last Update Posted: January 23, 2018
Last Verified: January 2018

Keywords provided by Eisai Inc.:
Thrombocytopenia
chronic liver disease

Additional relevant MeSH terms:
Liver Diseases
Thrombocytopenia
Digestive System Diseases
Blood Platelet Disorders
Hematologic Diseases