Comparative Study of Entecavir vs Adefovir vs the Combination in Lamivudine- Refractory Chronic Hepatitis B Subjects The DEFINE Study Revised Protocol 01 - The DEFINE Study

• Conditions: CHRONIC HEPATITIS B VIRUS; MedDRA version: 9.1Level: LLTClassification code 10019731Term: Hepatitis B

• Registration Number: EUCTR2006-000422-31-IT
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-03
• Last Update Posted: 14 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 462

Inclusion Criteria

1 Signed written informed consent; 2 Subjects must have a history of previous lamivudine treatment, and must have LVD resistance substitutions at reverse transcriptase rtM204I/V rtL180M; 3 Subjects must be nucleoside- and nucleotide-na ve, except for lamivudine, and have chronic HBV infection detectable HBsAg at screening and at least 24 weeks prior to screening, or detectable HBsAg for 24 weeks and negative for IgM core antibody ; 4 Subjects must have compensated liver function and must meet ALL of the following criteria International Normalization Ratio INR 8804; 1.5 Serum albumin 8805; 3 g/dL 8805; 30 g/L Serum total bilirubin 8804; 2.5 mg/dL 8804; 42.75 mol/L 5 HBV DNA 8805; 172,000 IU/mL approximately 1,000,000 copies/mL by PCR at screening; 6 ALT 8805; 1.3 x the ULN at screening and at least once 8805; 12 weeks prior to screening; 7 Documentation of HBeAg-positive and HBeAb-negative status at screening and at least once 8805; 4 weeks prior to screening; 8 Males and females 8805; 16 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 does of investigational product; 2 WOCBP using a prohibited contraceptive method. At this time there are no known contraindicated contraceptives to entecavir or adefovir; 3 Women who are pregnant or breastfeeding; 4 Women with a positive pregnancy test on enrollment or prior to investigational product administration; 5 Sexually active fertile men not using effective birth control if their partners are WOCBP; 6 Evidence of decompensated cirrhosis including but not limited to variceal bleeding; hepatic encephalopathy; or ascites requiring management with diuretics or paracentesis; 7 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 ; 8 Recent history of pancreatitis within 24 weeks prior to the first dose of study medication ; 9 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; 10 Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications see Exclusion Criterion 19 ; 11 Serum creatinine 1.5 mg/dL; 12 Hemoglobin 10.0 g/dL; 13 Platelet count 70,000/mm ; 14 Absolute neutrophil count 1500 cells/mm ; 15 Serum alpha fetoprotein AFP level 100 ng/mL; 16 Known history of allergy to nucleoside or nucleotide analogues; 17 Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B e.g., adefovir, entecavir, famciclovir, tenofovir, telbivudine, clevudine, emtracitabine , or any other experimental anti-HBV antiviral; 18 Therapy with interferon; thymosin alpha or other immuno-stimulators within 24 weeks of randomization into this study; 19 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 ; 20 Prisoners or subjects who are compulsorily detained involuntarily incarcerated for treatment of either a psychiatric or physical e.g., infectious disease illness must not be enrolled into this study; 21 Unable to tolerate oral medication; 22 Poor peripheral venous access

Study & Design

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