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

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 \< 9.0 g/dL, absolute neutrophil count (ANC) \< 1 x 109/L (1000/mm3), platelet count \< 75 x 109/L (75 x 103/mm3), serum Creatinine \> 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