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

NCT00441974 | Completed Phase 4 Results

• 1 other identifier: ADF108356
• Study Type: interventional
• Target: 1,470
• Locations: 1 country
• Sites: 25

Brief 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.

Conditions

Chronic Hepatitis B

Keywords

adefovir dipivoxil; compensated; chronic hepatitis B; Chinese

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) <1000 Copies/Milliliter at Week 48

  HBV (Hepatitis B Virus) DNA level was tested by real-time Polymerase Chain Reaction at Week 48.

  Week 48

Secondary Outcomes (6)

• Number of HBeAg Positive Participants Achieving Histological Improvement at Week 48

  Week 48

• Ranked Assessment of Liver Histology in HBeAg Positive Participants From Baseline to Week 48

  Baseline to Week 48

• Change From Screening in Median Serum HBV DNA at Weeks 24 and 48

  Weeks 24 and 48

• Number of Participants Achieving ALT (Alanine Aminotransferase) Normalization at Week 48

  Week 48

• Number of HBeAg Positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Week 48

  Week 48

Study Arms (1)

Single arm adefovir dipivoxil

EXPERIMENTAL

adefovir dipivoxil once daily orally 10 mg

Drug: adefovir dipivoxil

Interventions

adefovir dipivoxil DRUG

adefovir dipivoxil once daily one tablet 10mg orally

Single arm adefovir dipivoxil

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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 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

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 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (25)

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, 210002, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210003, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, 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

Beijing, 100069, China

Location

GSK Investigational Site

Changsha, 410008, China

Location

GSK Investigational Site

Changsha, 410011, China

Location

GSK Investigational Site

Chongqing, 400038, China

Location

GSK Investigational Site

Chongquin, 400038, China

Location

GSK Investigational Site

Fuzhou, 350025, 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

GSK Investigational Site

Tianjin, 300192, 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: February 28, 2007
• First Posted: March 1, 2007
• Study Start: December 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: October 20, 2009
• Results First Posted: October 2, 2009

Record last verified: 2009-10

Locations

CN (25)