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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00324961
First received: May 9, 2006
Last updated: October 26, 2009
Last verified: October 2009
  Purpose

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


Condition Intervention Phase
Chronic Hepatitis B
Drug: adefovir dipivoxil tablets
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 2-year Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With HBe Antigen Negative Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Achieving HBV DNA ≤300 Copies/mL at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants Achieving Histological Improvement After the 104-week Treatment [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  • Liver Histology Scores in HBeAg Negative Participants With Two Sequential Liver Biopsies During the Period of 104 Weeks [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
  • Change From Baseline in Median Serum HBV DNA Over Time [ Time Frame: Baseline and Weeks 13, 26, 39, 52, 65, 78, 91, and 104 ] [ Designated as safety issue: No ]
  • Number of Participants Achieving ALT Normalization at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  • Number of Participants Achieving HBsAg Loss and HBsAg Seroconversion at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  • Number of Participants With ADV-associated Resistance at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  • Number of Participants Achieving HBV DNA ≤300 Copies/mL Over Time [ Time Frame: Weeks 13, 26, 39, 52, 65, 78, 91, and 104 ] [ Designated as safety issue: No ]
  • Number of Participants Achieving Complete Response at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  • Time to Protocol-defined Complete Response Over a 104-week Treatment Period [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]

Enrollment: 533
Study Start Date: January 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm open label adefovir dipivoxil
adefovir dipivoxil once daily 10 mg orally
Drug: adefovir dipivoxil tablets
adefovir dipivoxil once daily 10 mg orally
Other Name: adefovir dipivoxil tablets

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:
    • Absolute neutrophil count ≥ 1 x 10³/mm³ ( ≥ 1 x 10^9/L);
    • Platelets ≥ 80 x 10³/mm³ (≥ 80 x 10^9/L); Platelets ≥ 100 x 10³/mm³ ( ≥ 100 x 10^9/L) recommended for the patients who will undergo liver biopsy.
    • Hemoglobin ≥ 10 g/dL (≥ 100 g/L) (males) or ≥ 9 g/dL (≥ 9 g/L) (females).
    • Willing and able to undergo a minimum of two liver biopsies (prior to dosing, and after 104 weeks of therapy; only apply to subjects who are enrolled to the sites where liver biopsy is required).
    • A female is eligible to enter and participate in this study if she is of:

      1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal);
      2. child-bearing potential with a negative serum pregnancy test at screen, and agrees to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug, (a minimum of 5 half-lives or longer if the pharmacodynamic profile of the investigational drug warrants a longer time period); or, Female sterilization; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combined or progestogen only); or, Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, Any other methods with published data showing that the lowest expected failure rate for that method is less than 1% per year; or, Barrier method only if used in combination with any of the above acceptable methods.
    • Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this study
    • Able to give written informed consent and comply with the requirements of the study

Exclusion Criteria:

  • 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.
    • Received nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid) within 2 months prior to study screening or the expectation that patient will receive any of these during the course of the study.
    • Receiving systemic (intravenous or oral) steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
    • History of hypersensitivity to nucleoside and/or nucleotide analogues.
    • Inability to comply with study requirements.
    • Lactating females or females with a positive serum pregnancy test.
    • Organ or bone marrow transplant recipients.
    • Previous (or planned) participation in an investigational trial involving administration of investigational compound within 2 months prior to the study screening.
    • Can not comply with the requirements of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324961

Locations
China, Guangdong
GSK Investigational Site
Guangzhou, Guangdong, China, 510630
GSK Investigational Site
Guangzhou, Guangdong, China, 510515
China, Hubei
GSK Investigational Site
Wuhan, Hubei, China, 430030
China, Jiangsu
GSK Investigational Site
Nanjing, Jiangsu, China, 210029
China, Jilin
GSK Investigational Site
Changchun, Jilin, China, 130021
China, Zhejiang
GSK Investigational Site
Hangzhou, Zhejiang, China, 310003
China
GSK Investigational Site
Beijing, China, 100044
GSK Investigational Site
Beijing, China, 100050
GSK Investigational Site
Beijing, China, 100011
GSK Investigational Site
Changsha, China, 410008
GSK Investigational Site
Chongqing, China, 400038
GSK Investigational Site
Chongquin, China, 400038
GSK Investigational Site
Jinan, China, 250021
GSK Investigational Site
Shanghai, China, 200433
GSK Investigational Site
Shanghai, China, 200001
GSK Investigational Site
Shanghai, China, 200003
GSK Investigational Site
Shanghai, China, 200040
GSK Investigational Site
Shanghai, China, 200025
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00324961     History of Changes
Other Study ID Numbers: ADF106632
Study First Received: May 9, 2006
Results First Received: August 27, 2009
Last Updated: October 26, 2009
Health Authority: China: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
adefovir dipivoxil
e Antigen negative
chronic hepatitis B
Chinese

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir
Adefovir dipivoxil
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on August 21, 2014