Intervention: Tenofovir Disoproxil Fumarate
Trial phase: Phase 4
SMILES: CC(C)OC(=O)OCOP(=O)(COC(C)Cn1cnc2c(N)ncnc21)OCOC(=O)OC(C)C.O=C(O)C=CC(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 75
Group description: Participants with on-going ETV treatment were switched to TDF treatment on Day 1. Participants then started with TDF on the day ETV was discontinued, without any overlapping treatment periods. All participants received one tablet of TDF 300 milligram (mg) once daily orally for 96 weeks.
Eligibility criteria:
Inclusion Criteria:

Subjects must be 20 to 69 years of age inclusive, at the time of signing the informed consent

Male and female subjects. A female subject is eligible to participate if she is not pregnant and not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP), OR
A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 days after the last dose of study treatment
Capable of giving signed informed consent form (ICF)
Subjects with chronic hepatitis B (CHB) (excluding hospitalized subjects)
Subjects treated with ETV for at least 2 years prior to initiation of study treatment.
The serum HBV-DNA level at screening is below the limit of quantitation (< 2.1 Log10 copies/milliliter [mL] or < 20 international unit [IU]/mL).
Subjects with serum HBeAg positive at screening

Meet either of the following serum HBsAg levels at screening:

Serum HBsAg 80 < to < 800 IU/mL and fluctuation range is equal or more than -0.1 Log10 IU/mL per year
Serum HBsAg >=800 IU/mL

Meet all of the following criteria at screening:

Creatinine clearance (CLcr) >=70 mL/minute. CLcr is calculated using the following Cockcroft-Gault formula.

Male: CLcr = (body weight in kilogram [kg] multiplied by [140 minus age in years]) divided by (72 multiplied by serum creatinine [milligram {mg}/deciliter {dL}]) Female: CLcr = CLcr (male) multiplied by 0.85

Hemoglobin >= 8 gram/dL
WBC >=1000 per cubic millimeter (mm^3)

Exclusion Criteria:

QTc > 450 millisecond (msec) or > 480 msec for subjects with bundle branch block
Received any interferon or Hepatitis B vaccine therapy within 24 weeks prior to initiation of the study treatment.
Received overdose of nonsteroidal anti-inflammatory drugs (NSAIDs) (excluding temporary or topical use) within 7 days prior to initiation of the study treatment.

Received any of the following drugs within 8 weeks prior to initiation of the study treatment (excluding topical products such as ointment and/or cream etc).

Drugs causing renal impairment (examples: aminoglycosides, amphotericin B, vancomycin, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine, some contrast mediums [ionic high-osmolar contrast media, ionic low-osmolar contrast media]
Competitors of renal excretion (except temporary use, example: probenecid)
Immunosuppressants (examples: azathioprine, cycolphosphamide) or chemotherapeutics (example: etoposide)
Glucocorticoid preparation
Received TDF, Adefovir pivoxil (ADV) or Tenofovir Alafenamide Fumarate (TAF) within 2 years prior to initiation of the study treatment
Participation in another clinical study within 6 months prior to screening, or planned participation in another clinical study simultaneously with this study.
Co-infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
Subjects with serious complication other than compensated CHB (cancer, significant renal, cardiovascular, pulmonary, or neurological disease, uncontrollable diabetes, etc.)
Received or have a plan for solid organ or bone marrow transplantation
Has proximal tubulopathy.
Subjects with decompensated CHB who meet the following: direct bilirubin > 1.5 times upper limit of normal (ULN), Prothrombin Time (PT) < 60%, platelets < 75,000/mm3 and serum albumin < 3.0 g/dL
Autoimmune hepatitis (Antinuclear titer > 1:160), excluding CHB
Subjects with or suspected of having hepatocellular carcinoma (HCC) (including both primary and metastatic) from diagnostic imaging at screening, or with serum alpha-fetoprotein (AFP) > 50 nanogram (ng)/mL at screening
History of HCC (except subjects who underwent resection or received curative treatment by radiofrequency, and with AFP <=10 ng/mL at screening)
Woman who is pregnant, possibly pregnant, lactating or planning a pregnancy during the study period.
Psychiatry disorder or cognitive disorder that may affect the subject's ability to give informed consent or to follow specified study procedures.
Subjects with a history of alcohol or drug abuse
Subjects whom the investigator (or sub-investigator) considers ineligible for the study.
Subjects with hypersensitivity to study treatments or their components, nucleoside and/or nucleotide analogues. Subjects with drug allergy that, in the investigator's (sub-investigator's) [or medical monitor's] opinion, labeled contraindication for participation in the study, or other allergy.