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Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B

Primary Purpose

Hepatitis B, Chronic Hepatitis B

Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Entecavir
Telbivudine
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B focused on measuring HBeAg-positive, chronic hepatitis B, telbivudine, entecavir, viral kinetics

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female, 18-70 years of age with documented compensated hepatitis B "e" antigen (HBeAg)-positive chronic hepatitis B
  • Able to comply with study regimen and provide written informed consent

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Unwilling to use double barrier method of contraception
  • Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
  • Received Hepatitis B therapy in the past
  • Use of immunomodulatory therapy in past 12 months
  • History of or symptoms of hepatic decompensation or pancreatitis
  • Frequent or prolonged use of potentially hepatotoxic or nephrotoxic drugs
  • Concurrent medication likely to preclude compliance with schedule of evaluations
  • Use of other investigational drugs within 30 days of enrollment
  • Abnormal laboratory values during screening

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Holy Family Hospital_Bucheon
  • Inje University Busan Paik Hospital
  • Yeungnam University Medical Center
  • Gachon Univ. Gil Medical Center Hospital
  • Asan Medical Center
  • Kangnam Sacred Heart Hospital
  • Korea University Medical Center_Anam
  • The Catholic University of Korea

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Telbivudine

Entecavir

Arm Description

Outcomes

Primary Outcome Measures

Change in Mean Hepatitis B Virus (HBV) DNA Levels
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.

Secondary Outcome Measures

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.
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.
Change in Alanine Aminotransferase (ALT) Levels
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.
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.
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.
Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative
PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL.

Full Information

First Posted
December 15, 2006
Last Updated
February 23, 2015
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00412529
Brief Title
Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B
Official Title
A Randomized, Open-label, Controlled, Multicenter, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine (LDT600) 600 mg or Entecavir (ETV) 0.5 mg Given Over 12 Weeks on the Kinetics of Hepatitis B Virus (HBV) DNA in Adults With HBeAg-positive, Compensated Chronic Hepatitis B (CHB)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic Hepatitis B
Keywords
HBeAg-positive, chronic hepatitis B, telbivudine, entecavir, viral kinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Telbivudine
Arm Type
Experimental
Arm Title
Entecavir
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
Entecavir 0.5 mg once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Telbivudine
Intervention Description
Telbivudine 600 mg once daily for 12 weeks.
Primary Outcome Measure Information:
Title
Change in Mean Hepatitis B Virus (HBV) DNA Levels
Description
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.
Time Frame
Baseline (day 1) to Week 12 (day 85)
Secondary Outcome Measure Information:
Title
Change in Mean HBV DNA Level
Description
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.
Time Frame
Baseline (day 1) to Weeks 2, 4, 8
Title
The Area Under the Curve (AUC) of HBV DNA Change.
Description
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.
Time Frame
From Baseline to Week 12
Title
Change in Alanine Aminotransferase (ALT) Levels
Time Frame
From Baseline to Week 12
Title
Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance
Description
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.
Time Frame
Baseline to 12 weeks
Title
Characterization of Very Early Viral Kinetics: Estimation of the Rate of Infected Cell Loss
Description
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.
Time Frame
Baseline to 12 weeks
Title
Characterization of Very Early Viral Kinetics: Estimation of the Efficiency Factor of Blocking Virus Production
Description
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.
Time Frame
Baseline to 12 weeks
Title
Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative
Description
PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL.
Time Frame
At Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18-70 years of age with documented compensated hepatitis B "e" antigen (HBeAg)-positive chronic hepatitis B Able to comply with study regimen and provide written informed consent Exclusion Criteria: Pregnant or breastfeeding Unwilling to use double barrier method of contraception Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV) Received Hepatitis B therapy in the past Use of immunomodulatory therapy in past 12 months History of or symptoms of hepatic decompensation or pancreatitis Frequent or prolonged use of potentially hepatotoxic or nephrotoxic drugs Concurrent medication likely to preclude compliance with schedule of evaluations Use of other investigational drugs within 30 days of enrollment Abnormal laboratory values during screening Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Holy Family Hospital_Bucheon
City
Bucheon,Kyunggi
Country
Korea, Republic of
Facility Name
Inje University Busan Paik Hospital
City
Busan
Country
Korea, Republic of
Facility Name
Yeungnam University Medical Center
City
Daegu
Country
Korea, Republic of
Facility Name
Gachon Univ. Gil Medical Center Hospital
City
Incheon
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Kangnam Sacred Heart Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Korea University Medical Center_Anam
City
Seoul
Country
Korea, Republic of
Facility Name
The Catholic University of Korea
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
20028815
Citation
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.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826006/?tool=pubmed
Description
Early Viral Kinetics of Telbivudine and Entecavir: Results of a 12-Week Randomized Exploratory Study with Patients with HBeAg-Positive Chronic Hepatitis B

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Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B

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