study to assess the antiviral activity and safety endpoints for the treatment of besifovir 150mg compared to tenofovir 300mg in chronic hepatitis b patients who have resistance to nucleoside analogues

Conditions: Chronic Hepatitis B

Summary: to prove that a study drug is noninferior to a control drug with a proportion of subjects who showed hbv dna undetected (less than 400 copies/ml (69 iu/ml)) at the 48th week after 48-week administration of besifovir 150 mg, or tenofovir 300 mg as a control drug to chronic hepatitis b patients

* screening period subject registration is conducted with confirming selection and exclusion criteria after a written consent form is obtained within 42 days before clinical trial drug administration. * baseline subjects who visit on the date of starting clinical trial drug administration are randomized to a test group or a control group at a ratio of 1:1. double blindness is applied for both groups. * treatment period subjects are orally administered with a clinical trial drug q.ds.i.d. for 48 weeks and visit at the 0, 4th, 12th, 24th, 36th, and 48th week for an hbv dna test, laboratory tests, a physical test, vital signs, and adverse events. * follow-up period subjects are provided with appropriate treatment after completing the 48-week trial or dropping out. subjects visit once at the 60th week for follow-up of adverse events, such as acute deterioration of hepatitis b, and hbv dna test results. if any treatment is not conducted after 48-week administration, subjects visit at intervals of four weeks until a follow-up visit (60th week) and the same tests with the 24th week visit (visit 5) are conducted. however, subjects who participate in a 48-week separate extended trial conducted after 48-week administration in this clinical trial do not have a follow-up period.

Eligibility criteria:
inclusion criteria: * patients who show positive hbsag or has a history of chronic hepatitis b for the last six months or more before screening * patients who showed positive hbsag during screening * have developed nucleoside analogue resistant hb * had no received nucleotide analogue exclusion criteria: 1. treatment with pegylated interferons within 6 months 2. prior exposure to bsv 3. mutations conferring resistance to adv 4. serum hbv dna levels \< 69 iu/ml 5. coinfection with hepatitis c, hepatitis d or human immunodeficiency viruses 6. alt levels ≥ 10 x uln 7. evidence of decompensated liver disease (total bilirubin \> 2 x uln, prothrombin time \> 6 sec prolonged or inr \>1.5, serum albumin \<2.8 g/dl, uncontrolled ascites, overt hepatic encephalopathy, or child-pugh score ≥8) 8. certain laboratory abnormalities (hemoglobin \ 1.5 mg/dl, or serum amylase \> 2 x uln and lipase \> 2 x uln) 9. decreased estimated glomerular filtration rates \< 50 ml/min 10. presence of hepatocellular carcinoma or elevated alpha feto-protein \> 50 ng/ml 11. current use of aspirin or nonsteroidal anti-inflammatory drugs within 2 month 12. current use of immunosuppressive agents within 6 months 13. current use of high dose corticosteroids (prednisolone \> 20 mg/day or equivalent dose over 14 days) with 3 months 14. history of malignancy within 5 years 15. subjects who are participating in other clinical trials 16. pregnant or lactating women 17. hypersensitivity to the study drugs

Keywords: hbv