Clinical trial NCT00065507: Comparison of Entecavir to Adefovir in Chronic Hepatitis B Virus (HBV) Patients With Hepatic Decompensation
Official title: Comparison of the Efficacy and Safety of Entecavir Versus Adefovir in Subjects Chronically Infected With Hepatitis B Virus and Evidence of Hepatic Decompensation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B
Keywords: hepatic decompensation
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2003-07-29
Enrollment: 195
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase IIIb comparative study of entecavir 1.0 mg once daily (QD) vs. adefovir 10 mg QD in patients who have chronic hepatitis B infection and hepatic decompensation. The patients are treated for 96 weeks after the last subject is randomized.


Eligibility criteria: Inclusion

* Child-Pugh (CP) score \>= 7
* Hepatitis B virus (HBV) viremia

Exclusion

* Alanine aminotransferase (ALT) \> 15 x upper limit of normal (ULN)
* Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)/hepatitis D virus (HDV) coinfection

Primary outcomes:
measure: Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in HBV DNA by PCR at Week 48
timeFrame: Baseline, Week 48
measure: Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24
timeFrame: Week 24
measure: Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48
timeFrame: Week 48
measure: Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48
timeFrame: Week 24, Week 48
measure: Number of Subjects Achieving Composite Endpoint (HBV DNA < 10*4 Copies/mL by PCR Assay and Normal ALT [≤ 1.0 x ULN]) Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48
measure: >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48
measure: Change From Baseline in Child-Pugh Score Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48
timeFrame: Week 24, Week 48
measure: Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Improvement or No Worsening in MELD Score Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 48
measure: Mean Changes From Baseline in Quality of Life as Measured by the Short Form 36 (SF-36)
timeFrame: Baseline, Week 24, Week 48
measure: Mean Changes From Baseline in Quality of Life, as Measured by EuroQol-5D (EQ-5D) at Weeks 24 and 48
timeFrame: Baseline, Week 24, Week 48
measure: Change From Baseline in Albumin Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Mean Change From Baseline in Prothrombin Time Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Mean Change From Baseline in Total Bilirubin Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Change From Baseline in Platelet Count Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Participants Achieving Albumin Normalization Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Participants Achieving Prothrombin Time Normalization Through Week 48
timeFrame: Baseline, Week4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Participants Achieving Total Bilirubin Normalization Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Participants Achieving Platelet Count Normalization Through Week 48
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48
measure: Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48
timeFrame: Week 48
measure: Cumulative Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, HCC, Discontinuations Due to AEs, and Confirmed Creatinine Increase >=0.5 mg/dL
timeFrame: on-treatment events obtained after the start of therapy and no more than 5 days after the last dose of study therapy.
measure: Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data
timeFrame: Week 48=all on-treatment laboratory measurements up to Week 48. Cumulative data = on-treatment laboratory measurements obtained after the start of therapy and no more than 5 days after the last dose of study therapy.
measure: Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment
timeFrame: On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date.
measure: Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period
timeFrame: On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.
measure: Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up
timeFrame: On-treatment=up to Week 48 (Day 336); if discontinued early, all data up to 5 days after discontinuation date. 24-week follow-up=limited to end-of-dosing values and those from 6 days after last dose of study therapy to end of follow-up.
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Research And Education, Inc.
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Miami
country: United States
facility: University Of Miami School Of Medicine
state: Florida
city: Atlanta
country: United States
facility: Pediatric Gasteroenterology
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Medical Center East
state: Hawaii
city: Indianapolis
country: United States
facility: Indiana University Med Center
state: Indiana
city: Louisville
country: United States
facility: The Cht Liver Research Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System Irb
state: Michigan
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Medical Center (Cpmc)
state: New York
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: Ut Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Mcguire Dvamc
state: Virginia
city: Porto Alegre - Rs
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Sao Paulo - Sp
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Clichy Cedex
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Athens
country: Greece
facility: Local institution
city: Athens
country: Greece
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Thessaloniki
country: Greece
facility: Local Instituition
city: Thessaloniki
country: Greece
facility: Local Institution
city: Tai Po
country: Hong Kong
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Kolkata
country: India
facility: Local Institution
city: Lucknow
country: India
facility: Local Institution
city: New Delhi
country: India
facility: Local Institution
city: Jakarta
country: Indonesia
facility: Local Institution
city: Cebu
country: Philippines
facility: Local Institution
city: Manila
country: Philippines
facility: Local Institution
city: Bydgoszcz
country: Poland
facility: Local Institution
city: Chorzow
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Smolensk
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Observatory
country: South Africa
facility: Local Institution
state: Western Cape
city: Paarl
country: South Africa
facility: Local Institution
state: Western Cape
city: Changhua
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan
country: Taiwan
facility: Local Institution
city: Tianan
country: Taiwan
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
city: Hatyai
country: Thailand
facility: Local Institution
city: Adana
country: Turkey
facility: Local Institution
city: Izmir
country: Turkey
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: