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

February 23, 2015 updated by: Novartis Pharmaceuticals

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Bucheon,Kyunggi, Korea, Republic of
        • Holy Family Hospital_Bucheon
      • Busan, Korea, Republic of
        • Inje University Busan Paik Hospital
      • Daegu, Korea, Republic of
        • Yeungnam University Medical Center
      • Incheon, Korea, Republic of
        • Gachon Univ. Gil Medical Center Hospital
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • The Catholic University of Korea
      • Seoul, Korea, Republic of
        • KangNam Sacred Heart Hospital
      • Seoul, Korea, Republic of
        • Korea University Medical Center_Anam

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Entecavir
Drug: Entecavir
Entecavir 0.5 mg once daily for 12 weeks.
EXPERIMENTAL: Telbivudine
Drug: Telbivudine
Telbivudine 600 mg once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean Hepatitis B Virus (HBV) DNA Levels
Time Frame: Baseline (day 1) to Week 12 (day 85)
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.
Baseline (day 1) to Week 12 (day 85)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean HBV DNA Level
Time Frame: Baseline (day 1) to Weeks 2, 4, 8
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.
Time Frame: From Baseline to Week 12
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
Time Frame: From Baseline to Week 12
From Baseline to Week 12
Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance
Time Frame: Baseline to 12 weeks

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
Time Frame: Baseline to 12 weeks

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
Time Frame: Baseline to 12 weeks
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
Time Frame: At Week 12
PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL.
At Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (ACTUAL)

February 1, 2008

Study Registration Dates

First Submitted

December 15, 2006

First Submitted That Met QC Criteria

December 15, 2006

First Posted (ESTIMATE)

December 18, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

March 13, 2015

Last Update Submitted That Met QC Criteria

February 23, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLDT600A2407

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.

Clinical Trials on Hepatitis B

Clinical Trials on Telbivudine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cote d'Ivoire

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe