Clinical trial NCT00605384: A Phase IIIb Study to Compare Entecavir Plus Tenofovir vs. Adefovir Added to Continuing Lamivudine Therapy in Adult Patients With Lamivudine-Resistant Hepatitis B Infection
Official title: A Comparative Study of the Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Versus Adefovir Added to Continuing Lamivudine in Adults With Lamivudine- Resistant Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Hepatitis B
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-01-31
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to find out whether a combination of entecavir (ETV) plus tenofovir (TNF) works better against Hepatitis B virus than adefovir (ADV) added to continuing lamivudine (LVD) therapy in patients whose Hepatitis B virus (HBV) is resistant against lamivudine. The safety of this treatment will also be studied.


Eligibility criteria: Inclusion Criteria:

* Chronic HBV infection
* History of lamivudine (LVD) treatment, and lamivudine resistance (LVDr), receiving LVD at screening visit
* Compensated liver function
* HBV DNA ≥ 172,000 IU/mL
* Hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative

Exclusion Criteria:

* Evidence of decompensated cirrhosis
* Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
* Recent history of pancreatitis
* Serum alpha fetoprotein \> 100 ng/mL
* Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B

Primary outcomes:
measure: Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96
timeFrame: Week 96
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities
timeFrame: Day 1 through end of treatment (Week 100 +/- 5 days)
measure: Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96
timeFrame: Week 48, Week 96
measure: HBV DNA Values at Weeks 48 and 96
timeFrame: Weeks 48, Week 96
measure: Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96
timeFrame: Week 48, Week 96
measure: Number of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieved ALT Normalization (≤ 1 x ULN) at Weeks 48 and 96
timeFrame: Week 48, Week 96
measure: Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96
timeFrame: Baseline, Week 48, Week 96
measure: Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96
timeFrame: Baseline, Week 48, Week 96
measure: Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96
timeFrame: Week 48, Week 96
measure: Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96
timeFrame: Week 48, Week 96
measure: Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96
timeFrame: Week 48, Week 96
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New York
country: United States
facility: Local Institution
state: New York
city: Bruxelles
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Bonn
country: Germany
facility: Local Institution
city: Duesseldorf
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Messina
country: Italy
facility: Local Institution
city: Modena
country: Italy
facility: Local Institution
city: Naples
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: San Giovanni Rotondo
country: Italy
facility: Local Institution
city: Chorzow
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Ankara
country: Turkey
facility: Local Institution
city: Ankara
country: Turkey
facility: Local Institution
city: Istanbul
country: Turkey
facility: Local Institution
city: Istanbul
country: Turkey
facility: Local Institution
city: Istanbul
country: Turkey
facility: Local Institution
city: Istanbul
country: Turkey
facility: Local Institution
city: Istanbul
country: Turkey
facility: Local Institution
city: Izmir
country: Turkey
facility: Local Institution
city: Kocaeli
country: Turkey
facility: Local Institution
city: Sihhiye Ankara
country: Turkey
facility: Local Institution
city: Trabzon
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: