CHRONIC HEPATITIS B VIRUS MedDRA version: 9.1 Level: LLT Classification code 10019731 Term: Hepatitis B
Conditions
Interventions
Trade Name: Baraclude
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Entecavir
CAS Number: 209216-23-9
Current Sponsor code: BMS-200475-01
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the monotherapy treatment groups who achieve HBV DNA lt; 50 IU/mL approximately 300 copies/mL by PCR at Week 48 of treatment using the Roche COBAS TaqMan HBV Test for use with the High Pure System HPS assay.;Secondary Objective: Compare ETV ADV combination vs ETV ADV monotherapy for 1.Proportion of subjects - achieving HBV DNA 50 IU/mL by PCR at Wk 96 using the Roche COBAS TaqMan-HPS assay - achieving HBV DNA the lower limit of detection LLD for the Roche COBAS TaqMan-HPS assay Wk 48 96 - with HBV DNA in relevant categories using the Roche COBAS TaqMan-HPS assay Wk 48 96 - with ALT normalization Wk 48 96 - with HBeAg loss Wk 48 96 - with HBe seroconversion Wk 48 96 - with HBsAg loss and HBs seroconversion Wk 48 96 2.Mean log10 reduction from baseline in HBV DNA by PCR using the Roche COBAS TaqMan-HPS assay Wk 48 96 3. Frequency of AEs, SAEs, and study drug discontinuations due to AEs/laboratory abnormalities 4. Evaluate ETV resistance profile in combination therapy vs monotherapy;Primary end point(s): Primary Endpoint The proportion of subjects who achieve HBV DNA 50 IU/mL approximately 300 copies/mL by PCR at Week 48 of treatment using the Roche COBAS TaqMan HBV Test for use with the High Pure System HPS assay. | — |
Countries
Greece, Italy
Outcome results
None listed