A Double-Blind, Randomized, Parallel, Placebo-Controlled Phase III Study to Evaluate the Safety and Antiviral Activity of Clevudine 30 Mg QD in Patients Chronically Infected With Hepatitis B Virus
1. Patients who were between 18 and 60, inclusive.
2. Patients with HBV DNA ³1 x 106 copies/mL within 30 days of baseline.
3. Patients who were documented to be HBsAg positive for > 6 months. (The documentation
of positive HBsAg for the previous 6 months included previous laboratory reports of
HBsAg positive or HBeAg positive at least 6 month ago or IgM anti-HBc negative and
IgG anti-HBc positive at screening).
4. Patients who were HBeAg positive.
5. Patients with ALT levels which were in the range of ≥1.2 and < 15 times of the upper
limit of normal (x ULN) and bilirubin levels less than 2.0 mg/dL, prothrombin time of
less than 1.7 (INR), and a serum albumin level of at least 3.5 g/dL.
6. Women of child bearing potential with a negative serum (β-HCG) pregnancy test taken
within 14 days of starting therapy.
7. Patients who were able to give written informed consent prior to study start and to
comply with the study requirements.
1. Patients who were currently receiving antiviral, immunomodulatory or corticosteroid
2. Patients previously treated with lamivudine, lobucavir, famciclovir, adefovir or any
other investigational nucleoside for HBV infection.
3. Previous treatment with interferon that had ended less than 6 months prior to the
4. Patients with a history of ascites, variceal hemorrhage or hepatic encephalopathy.
5. Patients co-infected with HCV, HDV or HIV.
6. Patients with clinical evidence of liver mass or with alpha-fetoprotein > 50 ng/mL
7. Patients who were pregnant or breast-feeding.
8. Patients who were unwilling to use an “effective” method of contraception during the
treatment and for up to 3 months after cessation of therapy. For males, condoms
should be used. Females had to be surgically sterile (via hysterectomy or bilateral
tubal ligation) or post-menopausal or using at least medically acceptable barrier
method of contraception ( i.e. IUD, barrier methods with spermicide or abstinence)
9. Patients with a clinically relevant history of abuse of alcohol or drugs.
10. Patients with a significant gastrointestinal, renal, hepatic (decompensated),
bronchopulmonary, biliary diseases except asymptomatic GB stone, neurological,
cardiovascular, oncologic or allergic disease.
The patients with a benign tumor were excluded if judged by an investigator that the
continuation of study would be interfered by benign tumor.
11. Patients with creatinine clearance less than 60mL/min as estimated by the following
(140-age in years) (body weight [kg]) (72) (serum creatinine [mg/dL]) [Note: multiply
estimates by 0.85 for women]
Patients who were found to have YMDD HBV DNA polymerase mutation at baseline were to be
excluded from the overall efficacy evaluation and analyzed separately. They were to be
included in the overall safety evaluation.