None listed
Conditions
Interventions
Oral placebo for 8 weeks then alpha interferon 5-10 MU subcutaneously three times/week x 16 weeks, then no therapy x 24 weeks
Group name:Study group Type of group
Lobucavir 200 mg PO once daily (QD) for 48 weeks
Sponsors
BRISTOL MYERS SQUIBB COMPANY,
Eligibility
Inclusion criteria
Inclusion criteria: - Male and female subjects >16 years of age (>18 years of age in Estonia, Germany, Greece, Lithuania, Portugal, Slovak Republic, Spain and United Kingdom) with chronic hepatitis B infection who have not received more than 2 weeks of prior therapy with alpha interferon or other agents with activity against (e.g., adefovir, lamivudine, famciclovir or thymosin alpha). These agents might not have been received within 24 weeks of randomization into this study. - Documentation of chronic hepatitis B by ALL of the following measures: a) History of HBsAg in serum for >24 weeks. b) History of HBeAg in serum for >12 weeks. c) HBV DNA >3 MEq/mL (10.7 pg/mL) by the Chiron bDNA hybridization assay on two determinations at least 4 weeks apart. d) Liver biopsy demonstrating histopathology consistent with chronic hepatitis B within 52 weeks prior to randomization into this study. Subjects whose liver biopsy demonstrates cirrhosis are also eligible provided they have a well-compensated liver disease. - Subjects must have compensated liver disease according to the following criteria: a) Prothrombin time 3.0 g/dl c) Bilirubin < 2.5 mg/dl - ALT (SGPT) between the range of 1,5 to 10 x upper limit of normal on two determinations - AII women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 lU/L of b-hCG) within 48 hours prior to the start of study medication.
Exclusion criteria
Exclusion criteria: - Received immunosuppressive therapy (including systemic corticosteroids) or agents with activity against hepatitis B within 24 weeks prior to randomization into this study - Lipase >1.3 x upper limit of normal or clinical symptoms of pancreatitis or recent history of pancreatitis (within 24 weeks prior to randomization) - Serum alpha-fetoprotein level >20 ng/mL. Subjects with an elevated alpha-fetoprotein level between 21 and 100ng/mL may be enrolled if a repeat value obtained 4 weeks later does not demonstrate continuing rise of the alpha-fetoprotein level and if ultrasonography or computerized tomography (CT) of the liver performed prior to randomization into this study do not demonstrate a focal lesion suggestive of carcinoma - Previous treatment with lobucavir - Currently abusing alcohol or illegal drugs sufficient in the investigator’s opinion, to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity - History of a psychiatric condition, especially depression, since interferon may exacerbate these conditions - Sexually active subjects who are not surgically sterile and who are unwilling to practice a reliable method of contraception (approved oral, injectable or implantable contraceptive drug, intrauterine device (IUD), diaphragm or condom with spermicidal jelly or foam, or sexual abstinence) for the duration of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The proportion of subjects with undetectable levels of HBV DNA and HBeAg. Measure:Primary effectiveness criteria Timepoints:Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The proportion of subjects with undetectable levels of HBV DNA and HBeAg. Measure:Secondary effectiveness criteria Timepoints:Week 48 and 72 ; Outcome name:The proportion of subjects demonstrating an improvement histological activity (>2 point reduction in the score from baseline, as measured by the modified Knodell HAI scoring system). Measure:Secondary effectiveness criteria Timepoints:Week 24 and 48 ; Outcome name:The proportion of subjects in each group with normalization of serum ALT. Measure:Secondary effectiveness criteria Timepoints:Week 48 and 72 ; Outcome name:Occurrence of adverse clinical events and laboratory abnormalities. Measure:Safety criteria Timepoints:Throughout the study. | — |
Countries
Estonia, Germany, Greece, Lithuania, Peru, Portugal, Slovakia, Spain, United Kindgdom
Outcome results
None listed