Once-Daily Oral E5501 Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00914927
First received: June 4, 2009
Last updated: May 21, 2013
Last verified: January 2012
  Purpose

The purpose of this study is to evaluate the efficacy of once-daily Oral E5501 in subjects with chronic liver diseases and thrombocytopenia prior to elective surgical or diagnostic procedures, to evaluate the safety of short-term administration of E5501 and to evaluate the pharmacokinetics (PK) of E5501.


Condition Intervention Phase
Thrombocytopenia Related to Chronic Liver Disease
Drug: E5501
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Proportion of responders (i.e., a responder is defined as a subject having an increase of at least 20,000/mm^3 platelet count from baseline and a platelet count >50,000/mm^3, at least once during Day 4 through Day 8). [ Time Frame: Day 4 through Day 8. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in platelet count from baseline on Day 8 or at end of treatment; dose-response of E5501 for platelet count elevation; proportion of subjects who achieve a platelet count >75,000/mm^3 on Day 4. [ Time Frame: Day 4 through Day 8. ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve a platelet count >100,000/mm^3 on Days 4 and 8 [ Time Frame: Day 4 through Day 8. ] [ Designated as safety issue: No ]

Enrollment: 136
Study Start Date: May 2009
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: E5501
E5501 First Dose 80 mg followed by 10 mg a day for up to 6 additional days
Experimental: 2 Drug: E5501
E5501 First Dose 80mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days
Placebo Comparator: 3 Drug: Placebo
Placebo or inactive substance once a day for up to 7 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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%)/mm3)
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00914927     History of Changes
Other Study ID Numbers: E5501-G000-202
Study First Received: June 4, 2009
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Thrombocytopenia
chronic liver disease

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

ClinicalTrials.gov processed this record on September 29, 2014