- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00507507
A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
A Randomized, Double-Blind Study Evaluating Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus the Combination of Emtricitabine and Tenofovir DF for the Treatment of Chronic Hepatitis B
The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection.
The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters.
Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia, 2050
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Westmead, New South Wales, Australia, 2145
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Victoria
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Heidelburg, Victoria, Australia, 3081
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Melbourne, Victoria, Australia, 3004
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Alberta
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Calgary, Alberta, Canada, T2N4N1
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British Columbia
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Vancouver, British Columbia, Canada, V5Z1H2
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Ontario
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Toronto, Ontario, Canada, M5G 2C4
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Lille, France, 59037
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Lyon, France, 69288
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Strasbourg, France, 67091
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Berlin, Germany, 13353
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Berlin, Germany, 10969
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Duesseldorf, Germany, 40237
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Frankfurt, Germany, 60590
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Hamburg, Germany, 20251
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Hannover, Germany, 30623
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Heidelberg, Germany, 69120
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Herne, Germany, 44623
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Mainz, Germany, 55131
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Pokfulam, Hong Kong
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Shatin, Hong Kong
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Tai Po, Hong Kong
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Hamilton, New Zealand
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Auckland
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Grafton, Auckland, New Zealand, 1150
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Bydgoszcz, Poland, 85-030
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Chorzow, Poland, 41-500
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Warszawa, Poland, 01-201
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Singapore, Singapore, 119074
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Singapore, Singapore, 529889
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Kaohsiung, Taiwan, 807
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Kaoshiung, Taiwan, 833
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Tainan, Taiwan, 107
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Taipei, Taiwan
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London, United Kingdom, NW3 2QG
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Sheffield, United Kingdom, S10 2JF
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California
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Los Angeles, California, United States, 90048
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San Diego, California, United States, 92115
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San Francisco, California, United States, 11355
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Florida
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Miami, Florida, United States, 33136
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Michigan
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Detroit, Michigan, United States, 48202
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New York
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Manhasset, New York, United States, 11030
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New York, New York, United States, 10029-6574
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New York, New York, United States, 10021
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Tennessee
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Germantown, Tennessee, United States, 38138
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Washington
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Seattle, Washington, United States, 98111
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen
- 18 through 69 years of age, inclusive
- Hepatitis B e antigen (HBeAg) positive
- HBV DNA ≥ 10^8 copies/mL
- ALT ≤ the upper limit of the normal range (ULN)
- Willing and able to provide written informed consent
- Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)
- Calculated creatinine clearance ≥ 70 mL/min
- Hemoglobin ≥ 10 g/dL
- Neutrophils ≥ 1,500/mm^3
- No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
Exclusion Criteria:
- Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study
- Males and females of reproductive potential unwilling to use an effective method of contraception during the study
- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage)
- Received interferon (pegylated or not) therapy within 6 months of the screening visit
- Alpha-fetoprotein > 50 ng/mL
- Evidence of hepatocellular carcinoma
- Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
- Significant renal, cardiovascular, pulmonary, or neurological disease
- Received solid organ or bone marrow transplantation
- Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
- Had proximal tubulopathy
- Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Tenofovir DF
Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily.
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Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily
Other Names:
Placebo to match FTC taken once daily
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Experimental: FTC+Tenofovir DF
Participants were randomized to receive FTC plus tenofovir DF once daily.
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Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily
Other Names:
Emtricitabine (FTC) 200 mg capsule taken orally once daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
Time Frame: Week 192
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The percentage of participants with HBV DNA < 400 copies/mL at Week 192 was analyzed.
Participants with missing data were considered to have failed to achieve the criteria for evaluation.
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Week 192
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144
Time Frame: Weeks 48, 96, and 144
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The percentage of participants with HBV DNA < 400 copies/mL at Weeks 48, 96, and 144 was analyzed.
Participants with missing data were considered to have failed to achieve the criteria for evaluation.
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Weeks 48, 96, and 144
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Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192
Time Frame: Weeks 48, 96, 144, and 192
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The percentage of participants with HBV DNA < 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed.
Participants with missing data were considered to have failed to achieve the criteria for evaluation.
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Weeks 48, 96, 144, and 192
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Change From Baseline in HBV DNA at Week 48
Time Frame: Baseline to Week 48
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The change from baseline in HBV DNA at Week 48 was analyzed.
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Baseline to Week 48
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Change From Baseline in HBV DNA at Week 96
Time Frame: Baseline to Week 96
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The change from baseline in HBV DNA at Week 96 was analyzed.
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Baseline to Week 96
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Change From Baseline in HBV DNA at Week 144
Time Frame: Baseline to Week 144
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The change from baseline in HBV DNA at Week 144 was analyzed.
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Baseline to Week 144
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Change From Baseline in HBV DNA at Week 192
Time Frame: Baseline to Week 192
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The change from baseline in HBV DNA at Week 192 was analyzed.
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Baseline to Week 192
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Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192
Time Frame: Weeks 48, 96, 144, and 192
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Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males.
Participants with missing data were considered to have failed to achieve the criteria for evaluation.
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Weeks 48, 96, 144, and 192
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Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192
Time Frame: Weeks 48, 96, 144, and 192
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The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point. |
Weeks 48, 96, 144, and 192
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Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192
Time Frame: Weeks 48, 96, 144, and 192
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The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point. |
Weeks 48, 96, 144, and 192
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Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192
Time Frame: Weeks 48, 96, 144, and 192
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The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed.
Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
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Weeks 48, 96, 144, and 192
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Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192
Time Frame: Weeks 48, 96, 144, and 192
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The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed.
Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
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Weeks 48, 96, 144, and 192
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Occurrence of HBV Resistance Mutations
Time Frame: Baseline to Week 192
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The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192).
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Baseline to Week 192
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
Other Study ID Numbers
- GS-US-203-0101
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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