Safety and Antiviral Activity of Clevudine in Patients Infected With Hepatitis B Virus

Hepatitis B Clinical Trial

Official title:

A Double- Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Antiviral Activity of Clevudine 30 Mg QD and 50 Mg QD Doses in Patients Infected With Hepatitis B Virus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00305019
• Other study ID #: L-FMAU-201
• Status: Terminated
• Phase: Phase 2
• First received: March 17, 2006
• Last updated: April 11, 2006
• Start date: July 2002
• Est. completion date: March 2004

Study information

• Verified date: April 2006
• Source: Bukwang Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the antiviral effects and safety of clevudine 30 mg once a day (QD) and 50 mg QD in patients infected with hepatitis B virus (HBV).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 120
• Est. completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Patient who is between 18 and 60 years of age, inclusive

2. Patient who is HBV DNA positive with DNA levels at screening more than 3 x 10^6 copies/mL.

3. Patient who is documented to be hepatitis B surface antigen (HBsAg) positive for > 6 months. Patient is HBeAg positive and anti-HBe negative.

Evidence of HBsAg (+) for the previous 6 months may include the following:

• documentation of HBsAg (+) for the previous 6 months

• documentation of HBsAg (+) for the previous 3 months and IgM anti-HBc negative at screening

• IgM anti-HBc negative and IgG anti-HBc positive at screening

4. Patient who has ALT levels which are in the range of more than 2 to less than 10 times the upper limit of normal (x ULN) and bilirubin levels < 1.5 x ULN.

5. Female patient with a negative serum (HCG) pregnancy test taken within 14 days of starting therapy.

6. Patient who is able to give written informed consent prior to study start and to comply with the study requirements.

7. Patients who continue to meet the following criteria after completion of the Week 36 visit will have additional follow-up visits at Week 40, 44, 48:

• have received no additional therapy since completion of 12 weeks of treatment of L-FMAU and

• continue with period 1 log10 decrease in HBV DNA from baseline.

Exclusion Criteria:

1. Patient who is currently receiving antiviral, immunomodulatory or corticosteroid therapy.

2. Patients previously treated with lamivudine, lobucavir, adefovir or any other investigational nucleoside for HBV infection.

3. Patients with previous treatment with interferon that have ended less than 6 months prior to the screening visit.

4. Patient who has a history of ascites, variceal hemorrhage or hepatic encephalopathy.

5. Patient who is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV) or HIV.

6. Patient with clinical evidence of cirrhosis or hepatocellular carcinoma

7. Patient who is pregnant or breast-feeding.

8. Patient who is unwilling to use an “effective” method of contraception during the study and for up to 30 days after the use of study drug ceases. For males, condoms should be used. Females must be surgically sterile (via hysterectomy or bilateral tubal ligation), post-menopausal or using at least a medically acceptable barrier method of contraception (i.e., intrauterine device [IUD], barrier methods with spermicide or abstinence)

9. Patient who has a clinically relevant history of abuse of alcohol or drugs.

10. Patient who has a significant gastrointestinal, renal, hepatic (decompensated), bronchopulmonary, neurological, cardiovascular, oncologic or allergic disease.

11. Patient who has creatinine clearance less than 60 mL/min as estimated by the following formula:

(140-age in years) (body weight [kg])/ (72) (serum creatinine [mg/dL]) [Note: multiply estimates by 0.85 for women]

Patients found to have tyrosine, methionine, aspartate, aspartate (YMDD) HBV DNA polymerase mutation after the enrollment will be excluded from the efficacy evaluation but included in the safety evaluation.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Drug:
• clevudine

Locations

Country	Name	City	State
Korea, Republic of	Yongdong Severance Hospital	Dogok-dong	Kangnam-Gu, Seoul
Korea, Republic of	Kangdong Sacred Heart Hospital	Gil-dong	Kangdong-Gu, Seoul
Korea, Republic of	Korea University Guro Hospital	Guro-dong	Guro-ku, Seoul
Korea, Republic of	Samsung Medical Center	Ilwon-dong	Kangnam-Gu, Seoul
Korea, Republic of	Ewha Womans University Hospital	Mok-dong	Yangchon-Gu, Seoul
Korea, Republic of	Asan Medical Center	Pungnab2-dong	Songpa-Gu, Seoul
Korea, Republic of	Seoul National University	Yeongeon-dong	Jongno-Gu, Seoul
Korea, Republic of	St. Mary’s Hospital	Youido	Yougdungpo-Gu, Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Bukwang Pharmaceutical

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Change from baseline in HBV DNA (log10)
Secondary	Efficacy: Proportion of patients with HBV DNA below 1 pg/mL
Secondary	Proportion of patients with HBV DNA below the assay limit of detection (LOD) (SuperDigene HC test II LOD, <4,700 copies/mL)
Secondary	Proportion of patients with hepatitis Be antigen (HBeAg) loss
Secondary	Seroconversion rate (HBeAg loss and hepatitis Be antibody [HBeAb] positivity)
Secondary	Biochemical improvement (e.g., ALT normalization)
Secondary	Safety
Secondary	Laboratory tests
Secondary	Adverse Events
Secondary	Vital Signs
Secondary	Electrocardiogram (ECG)