Adefovir Dipivoxil For The Treatment Of Chinese Compensated Chronic Hepatitis B(CHB)Patients

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00441974
First received: February 28, 2007
Last updated: October 15, 2009
Last verified: October 2009
  Purpose

This 48-week open-label study of local manufactured adefovir dipivoxil Tablet evaluates the efficacy and safety of adefovir 10mg once daily in Chinese subjects with compensated CHB. Primary endpoint is proportion of subjects achieving HBV DNA undetectable (<=1000 copies/mL by by Roche COBAS AMPLICOR HBV MONITOR Test) at week 48. Approximately 1250 patients will be recruited in 30 study centers in China. The subjects are offered 48 weeks of open label adefovir dipivoxil treatment, with assessments every three months, after with is a 12-week post study treatment follow-up prior to study completion.


Condition Intervention Phase
Chronic Hepatitis B
Drug: adefovir dipivoxil
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 48-week Multi-centre, Open-label, Local Phase IV Study to Demonstrate the Efficacy and Safety of Adefovir Dipivoxil Tablets (10mg) in Chinese Subjects With Compensated Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change From Screening in Median Serum HBV DNA at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of Participants With ADV-associated Resistance at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Enrollment: 1470
Study Start Date: December 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm adefovir dipivoxil
adefovir dipivoxil once daily orally 10 mg
Drug: adefovir dipivoxil
adefovir dipivoxil once daily one tablet 10mg orally

  Eligibility

Ages Eligible for Study:   16 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 a least 6 months
  • Serum HBV DNA ≥105 copies/ml for HBeAg positive subjects or ≥104 copies/ml for HBeAg negative subjects (Real-time PCR, LLQ=1000cp/ml) at study screening (within 2 weeks before baseline), respectively.
  • ALT value ≥2 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 the study screening.
  • Compensated liver disease with the following laboratory and clinical parameters study screening:
  • prothrombin time ≤ 2 seconds above normal direct bilirubin
  • Albumin≥35g/L
  • Total bilirubin ≤2.5mg/dL (≤ 43 µmol/L) or normal direct bilirubin
  • No history of variceal bleeding
  • No history of encephalopathy
  • No history of ascites
  • Willing and able to undergo two liver biopsies (prior to dosing, and after 48 weeks of therapy; only apply to subjects who are enrolled to the sites where liver biopsy is required).
  • Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this study

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • 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 be eligible
  • co-infection with hepatitis delta (HDV)
  • co-infection with HIV
  • autoimmune hepatitis (antinuclear antibody titre>1:160)
  • Alanine aminotransferase(ALT) > 10 times ULN at screening or history of acute exacerbation leading to transient decompensation
  • Serum alpha fetoprotein (AFP) >50 ng/mL.
  • 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
  • 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)
  • Hemoglobin<12g/dL (120 g/L)(males) or <10 g/dL (100 g/L) (females)
  • 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 within the previous 6 months or during the study.
  • Use of chronic anti-viral agents(e.g. lamivudine, adefovir dipivoxil, entecavir, famciclovir, tenofovir, FTC, ganciclovir, DAPD, LfMA, HBIg, etc.), Chinese herbal medicines known to have activity against HBV within the previous 3 months or during the study; use of agents with effect of ALT reduction (e.g. schisandra agents) during 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.
  • 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.
  • Previous (or planned) participation in an investigational trial involving administration of investigational compound within 2 months prior to the study screening.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00441974

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, 210002
GSK Investigational Site
Nanjing, Jiangsu, China, 210029
GSK Investigational Site
Nanjing, Jiangsu, China, 210003
China, Jilin
GSK Investigational Site
Changchun, Jilin, China, 130021
China, Sichuan
GSK Investigational Site
Chengdu, Sichuan, China, 610041
China, Zhejiang
GSK Investigational Site
Hangzhou, Zhejiang, China, 310003
China
GSK Investigational Site
Beijing, China, 100011
GSK Investigational Site
Beijing, China, 100050
GSK Investigational Site
Beijing, China, 100069
GSK Investigational Site
Beijing, China, 100044
GSK Investigational Site
Changsha, China, 410008
GSK Investigational Site
Changsha, China, 410011
GSK Investigational Site
Chongqing, China, 400038
GSK Investigational Site
Chongquin, China, 400038
GSK Investigational Site
Fuzhou, China, 350025
GSK Investigational Site
Jinan, China, 250021
GSK Investigational Site
Shanghai, China, 200433
GSK Investigational Site
Shanghai, China, 200001
GSK Investigational Site
Shanghai, China, 200040
GSK Investigational Site
Shanghai, China, 200003
GSK Investigational Site
Shanghai, China, 200025
GSK Investigational Site
Tianjin, China, 300192
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00441974     History of Changes
Other Study ID Numbers: ADF108356
Study First Received: February 28, 2007
Results First Received: August 26, 2009
Last Updated: October 15, 2009
Health Authority: China: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
adefovir dipivoxil
compensated
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 April 15, 2014