- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00805675
Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
A Randomized, Open-label, Controlled, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine 600 mg and Tenofovir Disproxil Fumarate 300 mg in Combination or Telbivudine 600 mg or Tenofovir Disproxil Fumarate 300 mg Monotherapy Given Over 12 Weeks on the Kinetics of Hepatitis B Virus DNA in Adults With HBeAg Positive Compensated CHB
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Hong Kong, China
- Department of Medicine, Queen Mary Hospital
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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 negative for IgM anti-HBc and positive for IgG anti-HBc
- Age < 40 years old
- HBeAg positive
- HBV DNA > or = to 10^7 copies/mL by Abbott real-time PCR
- ALT < or = to 1 ULN
- Willing and able to provide written informed consent
- No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
- Is willing and able to comply with the study drug regimen and all other study procedures and requirements
- Is willing and able to provide written informed consent before any study assessment is perform
Exclusion Criteria:
- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 × ULN, PT > 1.2 × ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).
- Received interferon (pegylated or not) therapy within 6 months of the screening visit
- α-fetoprotein > 50 ng/mL
- Evidence of hepatocellular carcinoma (HCC)
- Co-infection with HCV (by serology), or HIV,
- Significant renal, cardiovascular, pulmonary, or neurological disease.
- Received solid organ or bone marrow transplantation.
- Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.
- Has proximal tubulopathy.
- Use of other investigational drugs at the time of enrollment, or within 30 days
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
- Is pregnant or breastfeeding.
- Is a women of child-bearing potential (WOCBP)unless post-menopausal or using one or more acceptable method of contraception.
- Patient has any other concurrent medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study.
- Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
- Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir.
Other protocol-defined inclusion/exclusion criteria may apply
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Telbivudine 600 mg monotherapy
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD.
Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit.
Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
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600 mg monotherapy supplied in film-coated tablets.
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Active Comparator: Tenofovir disproxil fumarate 300 mg monotherapy
All patients in this arm were randomized to receive Tenofovir disoproxil fumarate 300 mg(equivalent to tenofovir disoproxil 245 mg)QD.
Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit.
Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
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Tenofovir disoproxil fumarate was supplied in 300 mg tablets
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Active Comparator: Telbivudine 600 mg and Tenofovir 300 mg
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD and Tenofovir (TDF) 300 mg (equivalent to Tenofovir disoproxil 245 mg)QD.
Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit.
Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
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Telbivudine 600 mg and Tenofovir 300 mg were purchased in commercial packs.
Patients were instructed to take medication(s) orally every morning either with or without food.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
Time Frame: Baseline, Week 12
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Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.
Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL).
The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
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Baseline, Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.
Time Frame: Baseline, Week 2, Week 4, Week 8
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Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.
Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL).
The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
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Baseline, Week 2, Week 4, Week 8
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Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12
Time Frame: Week 12
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Polymerase Chain Reaction (PCR) Negative is defined as HBV DNA levels <25 copies/ml.
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Week 12
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Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12
Time Frame: Week 12
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HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline.
HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb).
HBeAg stands for hepatitis B "e" antigen.
This antigen is a protein from the hepatitis B virus that circulates in infected blood when the virus is actively replicating.
The presence of HBeAg suggests that the person is infectious and is able to spread the virus to other people.
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Week 12
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Characterization of Very Early Viral Kinetics Through Estimated Viral Load
Time Frame: Week 12
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The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss |
Week 12
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Characterization of Very Early Viral Kinetics Through Viral Clearance
Time Frame: Week 12
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The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss |
Week 12
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Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss
Time Frame: Week 12
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The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss |
Week 12
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Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production.
Time Frame: Week 12
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The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t) I(t) (1 ) (T I(t))V(t) I(t) where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise allinfected and uninfected target cells, and δ the rate of infected cell loss |
Week 12
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Characterization of Very Early Viral Kinetics Through Half-live of Free Virus
Time Frame: Week 12
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The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss |
Week 12
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary 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
Keywords
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
- 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
- Telbivudine
Other Study ID Numbers
- CLDT600AHK01
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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