A Comparative Study of the Antiviral Efficacy and Safety of Entecavir Plus Tenofovirversus Adefovir Added to Continuing Lamivudine in Adults with Lamivudine ResistantChronic Hepatitis B Virus Infection. Revised Protocol 02, incorporating protocol amendment 01 (v1.0, Date 03-Jan-2008), protocol amendment 02 (v1.0, Date 31-Jul-2008) and Administrative Letter 01 (Date 06-Jun-2008).

• Conditions: HEPATITIS B VIRUS; MedDRA version: 9.1Level: LLTClassification code 10008910Term: Chronic hepatitis B

• Registration Number: EUCTR2007-001269-14-DE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04-15
• Last Update Posted: 16 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

1) Signed Written Informed Consent
2) Subjects with chronic HBV infection (detectable HBsAg at screening and for at least
24 weeks prior to screening, or detectable HBsAg for < 24 weeks and negative for
IgM core antibody); subjects may be either HBeAg-positive or HBeAg-negative;
3) Subjects must have a history of previous lamivudine treatment, must have LVD
resistance substitutions at reverse transcriptase rtM204I/V ± rtL180M, documented
by INNO-Lipa HBV-DR assay, and must be receiving lamivudine at the screening
visit;
4) Subjects must have compensated liver function and must meet ALL of the following
criteria;
International Normalization Ratio (INR) = 1.5
Serum albumin = 3 g/dL (= 30 g/L)
Serum total bilirubin = 2.5 mg/dL (= 42.75 µmol/L)
5) HBV DNA = 172,000 IU/mL HBV DNA (approximately 106 copies/mL) by PCR at
screening;
6) ALT =10 x the ULN at screening;
7) Men and women, = 18 years of age (or minimum age of consent in a given country).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 6 weeks after the last dose of
investigational product.
2) Evidence of decompensated cirrhosis including but not limited to: variceal bleeding;
hepatic encephalopathy; or ascites requiring management with diuretics or
paracentesis;
3) Coinfection with HIV, hepatitis C virus ([HCV]; coinfection is defined as HCV
Ab-positive with detectable HCV ribonucleic acid [RNA] by PCR), or hepatitis D
virus (HDV).
4) Recent history of pancreatitis (within 24 weeks prior to the first dose of study
medication);
5) Currently abusing illegal drugs or alcohol sufficient in the Investigator’s opinion, to
prevent adequate compliance with study therapy or to increase the risk of
hepatotoxicity or pancreatitis;
6) Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications (see Exclusion
Criteria 13 - 15).
7) Renal impairment that precludes subject from tolerating the per protocol study drug dose levels (see Protocol section 5.3.1).
8) Serum creatinine > 1.5 mg/dL;
9) Hemoglobin < 10.0 g/dL;
10) Platelet count < 70,000/mm3;
11) Absolute neutrophil count < 1500 cells/mm3;
12) Serum alpha fetoprotein (AFP) level > 100 ng/mL.
13) Known history of allergy to nucleoside or nucleotide analogues.
14) Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, entecavir, famciclovir,
tenofovir/emtricitabine, clevudine);
15) Therapy with interferon, thymosin alpha or other immuno-stimulators within
24 weeks of randomization into this study;
16) Required chronic administration of medications which cause immunosuppression or which are associated with a high risk of nephrotoxicity or hepatotoxicity or which
affect renal excretion. (See Protocol Section 5.5.1 for examples.).
17) Prisoners or subjects who are involuntarily incarcerated;
18) Subject who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease);
19) Unable to tolerate oral medication;
20) Poor peripheral venous access;
21) Off lamivudine therapy for greater than 7 days between the time of the screening visit and initiation of study treatment.

Subjects may be re-screened twice (for a total of three screens) if it can be reasonably expected that study criteria will be met. However, beyond this, subjects should be reevaluated only after consultation with the study team.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified