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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441974
• Other study ID #: ADF108356
• Status: Completed
• Phase: Phase 4
• First received: February 28, 2007
• Last updated: October 15, 2009
• Start date: December 2006
• Est. completion date: September 2008

Study information

• Verified date: October 2009
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1470
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• adefovir dipivoxil
adefovir dipivoxil once daily one tablet 10mg orally

Locations

Country	Name	City	State
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Changsha
China	GSK Investigational Site	Changsha
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Chongquin
China	GSK Investigational Site	Fuzhou
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Hangzhou	Zhejiang
China	GSK Investigational Site	Jinan
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48		Week 48	No
Secondary	Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48		Week 48	No
Secondary	Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48		Baseline to Week 48	No
Secondary	Change From Screening in Median Serum HBV DNA at Weeks 24 and 48		Weeks 24 and 48	No
Secondary	Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48		Week 48	No
Secondary	Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48		Week 48	No
Secondary	Number of Participants With ADV-associated Resistance at Week 48		Week 48	No