Overview

This trial is active, not recruiting.

Condition hepatitis b
Treatments tenofovir disoproxil fumarate (tdf) tablets, adefovir dipivoxil (adv) tablets
Phase phase 3
Sponsor GlaxoSmithKline
Start date March 2011
End date October 2012
Trial size 512 participants
Trial identifier NCT01300234, 114648

Summary

This is a multi-centre, double blind, double dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. This study is designed to demonstrate the superiority of TDF 300mg QD over ADV 10mg QD in treating Chinese subjects with CHB (hepatitis B e antigen [HBeAg] positive subjects and HBeAg negative subjects). It will also provide long-term efficacy and safety data (up to 240 weeks) for TDF 300 mg administered once daily.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Tenofovir disoproxil fumarate (TDF) tablets
tenofovir disoproxil fumarate (tdf) tablets TDF tablet
white, almond-shaped, film-coated tablets containing 300mg of TDF
(Active Comparator)
Adefovir dipivoxil (ADV) tablets
adefovir dipivoxil (adv) tablets ADV tablet
white to off-white, round, biconvex tablets containing 10mg of ADV

Primary Outcomes

Measure
Participants With Hepatitis B Virus (HBV) DNA <400 Copies/Milliliter (mL) at Week 48
time frame: Week 48

Secondary Outcomes

Measure
Participants With HBV DNA <400 Copies/mL at Weeks 96, 144, 192, and 240
time frame: Weeks 96, 144, 192, and 240
Log 10 Copies/mL Reduction From Baseline HBV DNA at Week 48
time frame: Baseline and Week 48
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 in Participants Who Had Abnormal ALT at Baseline
time frame: Baseline and Week 48
Number of Participants With Histological Improvement at Week 48 Who Had a Baseline Knodell Necroinflammatory Score (KNS) >=2
time frame: Baseline and Week 48
Number of HBeAg-positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Weeks 24 and 48
time frame: Week 24 and 28
Number of HBeAg-positive Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 24 and 48
time frame: Weeks 24 and 48
Number of HBeAg-negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 24 and 48
time frame: Weeks 24 and 48
Number of Participants Achieving Durable HBsAg Loss From Weeks 24 to Week 48
time frame: Week 24 to Week 48
Number of Participants With Virological Breakthrough at Week 48
time frame: Week 48
Number of Participants With Any Serious Adverse Event (SAE) and Any Adverse Event (AE)
time frame: up to Week 48
Number of Participants With the Indicated Grade 3 and Grade 4 Treatment-emergent (TE) Laboratory Abnormalities (LAs)
time frame: Baseline; up to Week 48/Early Withdrawal
Number of Participants With the Indicated Treatment-emergent Laboratory Abnormalities for Serum Creatinine and Serum Phosphorus
time frame: up to Week 48/Early Withdrawal
Number of Participants in the Indicated Category for Hepatic Laboratory Abnormalities
time frame: Baseline; up to Week 48/Early Withdrawal

Eligibility Criteria

Male or female participants from 18 years up to 69 years old.

Inclusion Criteria: - HBeAg positive/negative CHB with blood HBVDNA≥10^5 copies/mL and elevated ALT - Nucleoside and nucleotide naïve CHB subjects. Previous lamivudine treatment is allowed in less than 10% of the total study population Exclusion Criteria: - subjects with hepatocellular carcinoma (HCC) potential or decompensated liver disease - subjects with acute liver disease due to other causes - subjects with medication history of immunosuppressive therapy, immunomodulatory therapy, systemic cytotoxic agents, chronic antiviral agents including Chinese herbal medicines known to have activity against HBV (e.g., lamivudine, hepatitis B immunoglobulin (HBIg)) within the previous 6 months prior to randomisation into this study

Additional Information

Official title A Multi-centre, Double Blind, Double Dummy, Randomised, Controlled Study to Evaluate the Efficacy and Safety of TDF 300mg Once Daily (QD) Versus Adefovir Dipivoxil (ADV) 10mg QD in Chinese Subjects With CHB
Description This is a multi-centre, double-blind, double-dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. Four hundred and ninety-four subjects with CHB (200 HBeAg positive subjects and 294 HBeAg negative subjects) will be randomised (1:1ratio) to either TDF 300mg QD or ADV 10mg QD treatment arms. The primary endpoint is the proportion of subjects with blood hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <400copies/mL (Roche COBAS Taqman HBV test) at Week 48 in HBeAg positive subjects with CHB and HBeAg negative subjects with CHB. This is a two-part study. The first treatment period (baseline to Week 48) will investigate the effects of TDF and ADV on safety and efficacy endpoints; dosing will be double-blind. This period will be followed by 192 weeks in which all subjects will receive open-label TDF (Week 49 to Week 240). Subjects will undergo regular safety and efficacy assessments every 4 weeks for the first 12 weeks followed by every 12 weeks for a total of up to 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in September 2013.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.