Clinical trial NCT00313287: Safety and Antiviral Activity Study of Clevudine 30 mg QD in Patient With Chronic HBV
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatitis B
Lead sponsor: Bukwang Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2006-04-12
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine safety and efficacy of 30 mg daily dose of clevudine (L-FMAU) at 24 weeks of treatment in patients with chronic HBV.


Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

1. Patients who were currently receiving antiviral, immunomodulatory or corticosteroid therapy.
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 screening visit.
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 formula :

(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.

Primary outcomes:
measure: Efficacy:change from baseline in HBV DNA (log10) at Week 24
measure: Safety: clinically measured adverse events, abnormality of laboratory tests and abnormality of vital signs.
Secondary outcomes:
measure: Efficacy:
measure: Proportion of patients with HBV DNA below the assay Limit of Detection
measure: Proportion of patients with HBeAg loss and/or seroconversion (HBeAg loss and HBeAb gain)
measure: Proportion of ALT normalization
Other outcomes:
Locations:
city: Bupyoung-dong
country: Korea, Republic of
facility: St. Mercy's Hospital
state: Bupyoung-gu, Incheon
city: Pyoung-dong
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
state: Chongro-gu, Seoul
city: Jung-gu
country: Korea, Republic of
facility: Keimyumg University Dongsan Medical Center
state: Daegu
city: Jung-gu
country: Korea, Republic of
facility: Kyungpook National University Medical Hospital
state: Daegu
city: Hak-1-dong
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Dong-gu, Gwangju-si
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Gro-gu
city: Iksan-City
country: Korea, Republic of
facility: Wonkwang University Hospital
state: Jeonbuk
city: Jeonju-city
country: Korea, Republic of
facility: Chonbuk National University Hospital
state: Jeonbuk
city: Daesa-dong
country: Korea, Republic of
facility: Chungnam National University Hospital
state: Jung-gu, Daechon
city: Sinhung-dong
country: Korea, Republic of
facility: Inha University Hospital
state: Jung-gu, Incheon
city: Dogok-dong
country: Korea, Republic of
facility: Yongdong Severance Hospital
state: Kangnam-gu, Seoul
city: Pungnap-dong
country: Korea, Republic of
facility: Seoul Asan Medical Center
state: Kangnam-gu, Seoul
city: Ilsan-gu,
country: Korea, Republic of
facility: National Cancer Center
state: Kyounggi-do
city: Pucheon
country: Korea, Republic of
facility: St. Holly Family Mary's Hospital
state: Kyounggi-do
city: Seongnam-gu
country: Korea, Republic of
facility: Pochon CHA University Hospital
state: Kyounggi-do
city: Dae myoung-dong
country: Korea, Republic of
facility: Yeungnam University Medical Center
state: Nam-gu, Taegu
city: Gongneung-dong
country: Korea, Republic of
facility: Korea Cancer Center Hospital
state: Nowon-gu, Seoul
city: Hagye 1-dong
country: Korea, Republic of
facility: Nowon Eulji Hospital
state: Nowon-gu, Seoul
city: Ji-dong,
country: Korea, Republic of
facility: St. Vincent's Hospital
state: Paldal-gu, Suwon
city: Gaegeum-dong
country: Korea, Republic of
facility: Pusan Paik Hospital
state: Pusan
city: Ami-dong
country: Korea, Republic of
facility: Pusan National University Hospital
state: Seo-gu, Pusan
city: Amnam-dong
country: Korea, Republic of
facility: Kosin Medical Center
state: Seo-gu, Pusan
city: Banpo-dong
country: Korea, Republic of
facility: KangNam St. Mary's Hospital
state: Seocho-gu, Seoul
city: Shinchon- dong
country: Korea, Republic of
facility: Severance Hospital
state: Seodaemun-gu, Seoul
city: Jeo-dong
country: Korea, Republic of
facility: Seoul Paik Hospital
state: Seoul
city: Ilwon-dong
country: Korea, Republic of
facility: Samsung Medical Center
state: Songpa-gu, Seoul
city: Anam-dong
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Sungbuk-ku, Seoul
city: Mok-dong
country: Korea, Republic of
facility: Ehwa Womans University Mokdong Hospital
state: Yangcheon-gu, Seoul
city: Daelim-dong
country: Korea, Republic of
facility: Kangnam Sacred Heart Hospital
state: Yongdeungpo-gu, Seoul
city: Hannam-dong
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital
state: Yongsan-gu, Seoul
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital
state: Yungdungpo-Gu
city: Incheon
country: Korea, Republic of
facility: Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Hyo-Suk Lee, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References: