Study of Adefovir Dipivoxil for Korean Patients With Chronic Hepatitis B(CHB) Who Have Completed ADF 103814

A Phase IV, Open Label, Single Arm, Multicenter, Extension Study of Adefovir Dipivoxil for Korean Patients With Chronic Hepatitis B(CHB) Who Have Completed ADF 103814

This is an open label, single-arm, multi-centre extension study for Korean patients with chronic hepatitis B and compensated liver disease who have completed one-year adefovir dipivoxil treatment in ADF103814. The objective is to assess clinical efficacy and safety of long term (up to 3 years) adefovir dipivoxil 10mg therapy.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B; Hepatitis B, Chronic
• Intervention / Treatment: Drug: adefovir dipivoxil 10mg

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subject has completed ADF103814 and continues with adefovir dipivoxil treatment via prescription without interruption prior enrolment in this extension study.

Availability and willingness of subject to provide written informed consent.

Exclusion Criteria:

Use of immunosuppressive therapy requiring use of more than 5mg of prednisolone(or equivalent) per day, immunomodulatory therapy (including interferon or thymosin) or systemic cytotoxic agents during the study.

Previous or current lamivudine or antiviral therapy Clinical signs of decompensated liver disease as indicated by the protocol Inadequate haematological function defined by the protocol - Documented evidence of active liver disease due to other causes Hepatocellular carcinoma as evidenced by the protocol Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol. This would include any uncontrolled clinically significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders or cancer.

Active alcohol or drug abuse or history of alcohol or drug abuse considered by the investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results.

Planned for liver transplantation Therapy with nephrotoxic drugs or competitors of renal excretion can be expected during the course of the study.

History of hypersensitivity to nucleoside and/or nucleotide analogues. Inability to comply with study requirements as determined by the study investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatitis B Virus (HBV) DNA (log10 Copies/mL) Change From Baseline at Week 156 of Adefovir Therapy	HBV DNA was tested with Roche Cobas Amplicor HBV monitor test, Lower Limit of Detection 300 copies/mL) after 3 years (156 weeks: Weeks 1-52 in Study ADF103814; Weeks 53-156 in Study 108005) of adefovir therapy). Change from baseline was calculated as the Week 156 value minus the Baseline value. Baseline is defined as the first day of study ADF103814, of which Study 108005 is an extension.	Baseline, Week 156

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving ALT Normalization at Week 104 & 156	Alanine aminotransferase (ALT) normalization is defined as a value <= upper limit of normal (ULN) range based on the set of subjects with ALT>ULN at baseline. The normal range for ALT is 0-40 Units/Liter.	Week 104, Week 156
Number of Participants Achieving Virological Response at Week 104 & 156	Virological response is defined as HBV DNA level<300 copies/ml	Week 104, Week 156
HBV DNA Levels at Each Collection Time Point From Baseline Through Week 156	Serum HBV DNA. Baseline is defined as the first day of study ADF103814, of which Study 108005 is an extension.	Baseline, Weeks 68, 80, 92, 104, 120, 132, 144, 156
Number of Participants With HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion at Week 104 & 156	Hepatitis B e antigen (HBeAg) loss, HBeAg seroconversion (defined as HBeAg negative and hepatitis B e antibody [HBeAb] positive), hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion (defined as HBsAg negative and hepatitis B surface antibody [HBsAb] positive). HBeAg and HBsAg seroconversion are defined as the loss (becoming negative) of HBeAg and the concurrent appearance of antibodies against HBeAg and the loss of HBsAg and the concurrent appearance of antibodies against HBsAg, respectively.	Week 104 and 156
Safety Assessment: Number of Participants With a Serious Adverse Event and an Adverse Event	The number of participants with a serious adverse event and an adverse event is reported. Refer to the adverse event section for details.	Treatment Phase (Weeks 53-156)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, M.D., Ph.D, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): April 1, 2008

Study Registration Dates

• First Submitted: November 23, 2006
• First Submitted That Met QC Criteria: November 23, 2006
• First Posted (ESTIMATE): November 27, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): December 15, 2010
• Last Update Submitted That Met QC Criteria: November 24, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Adefovir Dipivoxil(Hepsera); Chronic Hepatitis B (CHB)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: ADF108005; update with ADF103814