Adefovir Dipivoxil Tablets (10mg) In Chinese Subjects With HBe Antigen Negative Chronic Hepatitis B

NCT00324961 | Completed Phase 4 Results

• 1 other identifier: ADF106632
• Study Type: interventional
• Target: 533
• Locations: 1 country
• Sites: 18

Brief Summary

This is a phase IV, 2-year, multi-center, single arm and open-label study, evaluating the efficacy and safety with using local manufactured adefovir dipivoxil in Chinese subjects with HBeAg negative chronic hepatitis B

Conditions

Chronic Hepatitis B

Keywords

adefovir dipivoxil; e Antigen negative; chronic hepatitis B; Chinese

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving HBV DNA ≤300 Copies/mL at Week 104

  Hepatitis B Virus (HBV) DNA level is tested in blood serum by real-time Polymerase Chain Reaction with the lower limit of detection (LLD) as 300 copies/milliliter in a central laboratory.

  Week 104

Secondary Outcomes (9)

• Number of Participants Achieving Histological Improvement After the 104-week Treatment

  Week 104

• Liver Histology Scores in HBeAg Negative Participants With Two Sequential Liver Biopsies During the Period of 104 Weeks

  Baseline to Week 104

• Change From Baseline in Median Serum HBV DNA Over Time

  Baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104

• Number of Participants Achieving ALT Normalization at Week 104

  Week 104

• Number of Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 104

  Week 104

Study Arms (1)

Single arm open label adefovir dipivoxil

EXPERIMENTAL

adefovir dipivoxil once daily 10 mg orally

Drug: adefovir dipivoxil tablets

Interventions

adefovir dipivoxil tablets DRUG

adefovir dipivoxil once daily 10 mg orally

Single arm open label adefovir dipivoxil

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18-65 years inclusive
• Documented chronic hepatitis B infection determined by the presence of serum HBsAg for at least 6 months
• Documented HBeAg negative and HBeAb positive at the screening visit and with at least a 6 months history of HBeAg negativity.
• Serum HBV DNA ≥ 104 copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD 300 copies/mL) at study screening (within 4 weeks before baseline)
• ALT value ≥1.3 times the upper limit of normal (ULN) at the time of screening, as determined using laboratory ranges and documented ALT abnormal within 6 month prior to the study screening.
• Serum alpha fetoprotein (AFP) \< 50 ng/mL at the first screening visit. If the AFP level is ≥ 50 ng/mL but declined to \< 50 ng/mL between screening and baseline, the patient is eligible.
• Compensated liver disease with the following laboratory and clinical parameters at study screening:
• Prothrombin time ≤ 2 second above normal range.
• Albumin ≥ 35 g/L.
• Total bilirubin ≤ 2.5 mg/dL (≤ 43 µmol/L) or normal direct bilirubin.
• No history of variceal bleeding.
• No history of encephalopathy.
• No history of ascites
• Adequate renal function defined as serum creatinine ≤ 1.5 mg/dL (≤ 130 µmol/L).
• Adequate hematological function defined as:

You may not qualify if:

• 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, may not limit to, renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, active infection or cancer.
• Documented evidence of active liver disease due to other causes including co-infection hepatitis C (HCV), Subjects who are anti-HCV positive and in whom HCV RNA is undetectable are considered to be HCV seropositive and will not eligible; co-infection with hepatitis delta (HDV); co-infection with HIV; autoimmune hepatitis (antinuclear antibody titre \> 1:160)
• Clinical signs of decompensated liver disease at baseline. These may include but are not limited to:
• serum bilirubin \> 2.5 mg/dL (≤ 43 µmol/L) - prothrombin time \> 2 second prolonged above ULN
• serum albumin \< 35g/L
• history of ascites, variceal bleeding, or encephalopathy
• Alanine aminotransferase (ALT) \>10 times ULN at screening or history of acute exacerbation leading to transient decompensation
• Hepatocellular carcinoma as evidenced by one of the following:
• suspicious foci on ultrasound or radiological examination
• \- where no positive ultrasound finding, but serum alpha-fetoprotein \> 100ng/mL
• 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.
• Use of immunosuppressive therapy, immunomodulatory therapy (including interferon or thymosin), systemic cytotoxic agents, chronic anti-viral agents excluding lamivudine (e.g. ganciclovir, adefovir dipivoxil, entecavir, famciclovir, FTC, DAPD, LFMAU, HBIg), Chinese herbal medicines known to have activity against HBV within the previous 12 months or during the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during the study
• Use of lamivudine within the previous 3 months or during the study
• Planned for liver transplantation or previous liver transplantation
• Received hepatotoxic drugs (e.g., anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin) within 2 months prior to study screening or expected to receive these during the course of the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (18)

GSK Investigational Site

Guangzhou, Guangdong, 510515, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510630, China

Location

GSK Investigational Site

Wuhan, Hubei, 430030, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310003, China

Location

GSK Investigational Site

Beijing, 100011, China

Location

GSK Investigational Site

Beijing, 100044, China

Location

GSK Investigational Site

Beijing, 100050, China

Location

GSK Investigational Site

Changsha, 410008, China

Location

GSK Investigational Site

Chongqing, 400038, China

Location

GSK Investigational Site

Chongquin, 400038, China

Location

GSK Investigational Site

Jinan, 250021, China

Location

GSK Investigational Site

Shanghai, 200001, China

Location

GSK Investigational Site

Shanghai, 200003, China

Location

GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Shanghai, 200433, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

adefovir dipivoxil

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 9, 2006
• First Posted: May 11, 2006
• Study Start: January 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: October 28, 2009
• Results First Posted: October 2, 2009

Record last verified: 2009-10

Locations

CN (18)