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This exploratory study is designed to determine the early viral kinetic profile during treatment with telbivudine or entecavir at multiple time points over 12 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Telbivudine | Experimental |
| |
| Entecavir | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entecavir | Drug | Entecavir 0.5 mg once daily for 12 weeks. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Hepatitis B Virus (HBV) DNA Levels | Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. | Baseline (day 1) to Week 12 (day 85) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean HBV DNA Level | Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.HBV DNA reductions, considered as the repeated measures, from baseline to Weeks 2, 4, 8. | Baseline (day 1) to Weeks 2, 4, 8 |
| The Area Under the Curve (AUC) of HBV DNA Change. |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Holy Family Hospital_Bucheon | Bucheon,Kyunggi | South Korea | ||||
| Inje University Busan Paik Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20028815 | Result | Suh DJ, Um SH, Herrmann E, Kim JH, Lee YS, Lee HJ, Lee MS, Lee YJ, Bao W, Lopez P, Lee HC, Avila C, Zeuzem S. Early viral kinetics of telbivudine and entecavir: results of a 12-week randomized exploratory study with patients with HBeAg-positive chronic hepatitis B. Antimicrob Agents Chemother. 2010 Mar;54(3):1242-7. doi: 10.1128/AAC.01163-09. Epub 2009 Dec 22. |
| Label | URL |
|---|---|
| Early Viral Kinetics of Telbivudine and Entecavir: Results of a 12-Week Randomized Exploratory Study with Patients with HBeAg-Positive Chronic Hepatitis B | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Telbivudine | Telbivudine 600 mg once daily for 12 weeks. |
| FG001 | Entecavir | Entecavir 0.5 mg once daily for 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Telbivudine | Telbivudine 600 mg once daily for 12 weeks. |
| BG001 | Entecavir | Entecavir 0.5 mg once daily for 12 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Baseline Measures based on Intention to treat population. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Mean Hepatitis B Virus (HBV) DNA Levels | Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. | Intent to Treat (ITT) population included all patients who received at least one dose of study drug and had at least one post-baseline assessment of serum HBV DNA. The randomized treatment was used in the analyses of this population. | Posted | Mean | Standard Deviation | log10 copies/mL | Baseline (day 1) to Week 12 (day 85) |
|
12 weeks
Safety population included all patients who received at least one dose of study drug and had at least one post-baseline safety assessment (i.e., adverse event or laboratory assessment).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Telbivudine | Telbivudine 600 mg once daily for 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest discomfort | General disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
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| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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| ID | Term |
|---|---|
| C413685 | entecavir |
| D000077712 | Telbivudine |
| ID | Term |
|---|---|
| D013936 | Thymidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| Telbivudine |
| Drug |
Telbivudine 600 mg once daily for 12 weeks. |
|
In AUC efficacy analyses, all the visits from baseline to Week 12 visit (including the planned and the repeated) with a non-missing HBV DNA level were included. |
| From Baseline to Week 12 |
| Change in Alanine Aminotransferase (ALT) Levels | From Baseline to Week 12 |
| Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance | Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-ε)pI(t) - cV(t) I(t) = (1- η)TV(t) - δI(t) V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data. | Baseline to 12 weeks |
| Characterization of Very Early Viral Kinetics: Estimation of the Rate of Infected Cell Loss | Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-ε)pI(t) - cV(t) I(t) = (1- η)TV(t) - δI(t) V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data. | Baseline to 12 weeks |
| Characterization of Very Early Viral Kinetics: Estimation of the Efficiency Factor of Blocking Virus Production | Viral kinetic parameters were estimated with a bi-phasic mathematical model of HBV DNA by using compartments of free virus, infected cells, and uninfected target cells. The model parameter of interest was the effectiveness of the drug in blocking virus production from infected cells (efficacy, ε). Blocking efficiency was within the range between 0 and 1. | Baseline to 12 weeks |
| Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative | PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL. | At Week 12 |
| Busan |
| South Korea |
| Yeungnam University Medical Center | Daegu | South Korea |
| Gachon Univ. Gil Medical Center Hospital | Incheon | South Korea |
| Asan Medical Center | Seoul | South Korea |
| Kangnam Sacred Heart Hospital | Seoul | South Korea |
| Korea University Medical Center_Anam | Seoul | South Korea |
| The Catholic University of Korea | Seoul | South Korea |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Change in Mean HBV DNA Level | Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.HBV DNA reductions, considered as the repeated measures, from baseline to Weeks 2, 4, 8. | Intent to Treat (ITT) population included all patients who received at least one dose of study drug and had at least one post-baseline assessment of serum HBV DNA. The randomized treatment was used in the analyses of this population. | Posted | Mean | Standard Deviation | log10 copies/mL | Baseline (day 1) to Weeks 2, 4, 8 |
|
|
|
| Secondary | The Area Under the Curve (AUC) of HBV DNA Change. | In AUC efficacy analyses, all the visits from baseline to Week 12 visit (including the planned and the repeated) with a non-missing HBV DNA level were included. | Intention-to-treat (ITT) population included all patients who received at least one dose of study drug and had at least one post-baseline assessment of serum HBV DNA. The randomized treatment was used in the analyses of this population. | Posted | Mean | Standard Deviation | (log10 copies/mL) * days | From Baseline to Week 12 |
|
|
|
| Secondary | Change in Alanine Aminotransferase (ALT) Levels | Intention to treat (ITT) population included all patients who received at least one dose of study drug and had at least one post-baseline assessment of serum HBV DNA. The randomized treatment was used in the analyses of this population. | Posted | Mean | Standard Deviation | IU/L | From Baseline to Week 12 |
|
|
|
| Secondary | Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance | Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-ε)pI(t) - cV(t) I(t) = (1- η)TV(t) - δI(t) V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data. | Intent to Treat (ITT) population. | Posted | Mean | Standard Deviation | clearance per day | Baseline to 12 weeks |
|
|
|
| Secondary | Characterization of Very Early Viral Kinetics: Estimation of the Rate of Infected Cell Loss | Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-ε)pI(t) - cV(t) I(t) = (1- η)TV(t) - δI(t) V serum viral load, I productively infected cells, ε efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, η efficiency factor of blocking de novo infection, β de novo infection rate, T uninfected target cells, δ rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data. | Intent to Treat (ITT) population. The value for the rate of infected cell loss for 1 patient in telbivudine arm was not used in calculation of summary statistics for this variable as this patient showed a deviation from the biphasic pattern in viral kinetic modeling. | Posted | Mean | Standard Deviation | infected cell loss per day | Baseline to 12 weeks |
|
|
|
| Secondary | Characterization of Very Early Viral Kinetics: Estimation of the Efficiency Factor of Blocking Virus Production | Viral kinetic parameters were estimated with a bi-phasic mathematical model of HBV DNA by using compartments of free virus, infected cells, and uninfected target cells. The model parameter of interest was the effectiveness of the drug in blocking virus production from infected cells (efficacy, ε). Blocking efficiency was within the range between 0 and 1. | Intent to Treat (ITT) population. | Posted | Mean | Standard Deviation | percentage of blocking efficiency | Baseline to 12 weeks |
|
|
|
| Secondary | Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative | PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL. | Intent to Treat (ITT) population included all patients who received at least one dose of study drug and had at least one post-baseline assessment of serum HBV DNA. The randomized treatment was used in the analyses of this population. | Posted | Number | Participants | At Week 12 |
|
|
|
| 1 |
| 23 |
| 4 |
| 23 |
| EG001 | Entecavir | Entecavir 0.5 mg once daily for 12 weeks. | 0 | 21 | 7 | 21 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006521 | Hepatitis, Chronic |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| Change from Baseline to week 8 : (N= 23, 21) |
|
| Change from Baseline to Week 12 |
|