Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B - Full Text View

Sponsor:	Novartis Pharmaceuticals
Collaborator:	Idenix Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00412529

Purpose

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.

Condition	Intervention	Phase
Hepatitis B Chronic Hepatitis B	Drug: Entecavir Drug: Telbivudine	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Entecavir Recombinant hepatitis B vaccine Hepatitis B Vaccines Hepatitis A Vaccines Telbivudine

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change in Mean Hepatitis B Virus (HBV) DNA Levels [ Time Frame: Baseline (day 1) to Week 12 (day 85) ] [ Designated as safety issue: No ]
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.

Secondary Outcome Measures:

Change in Mean HBV DNA Level [ Time Frame: Baseline (day 1) to Weeks 2, 4, 8 ] [ Designated as safety issue: No ]
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. [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL.

Enrollment:	44
Study Start Date:	December 2006
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Telbivudine	Drug: Telbivudine Telbivudine 600 mg once daily for 12 weeks.
Active Comparator: Entecavir	Drug: Entecavir Entecavir 0.5 mg once daily for 12 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00412529

Locations

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

Sponsors and Collaborators

Novartis Pharmaceuticals

Idenix Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

Additional Information:

Early Viral Kinetics of Telbivudine and Entecavir: Results of a 12-Week Randomized Exploratory Study with Patients with HBeAg-Positive Chronic Hepatitis B This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

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. Epub 2009 Dec 22.

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00412529 History of Changes
Other Study ID Numbers:	CLDT600A2407
Study First Received:	December 15, 2006
Results First Received:	December 2, 2010
Last Updated:	July 18, 2011
Health Authority:	Korea: Food and Drug Administration; United States: Food and Drug Administration

Keywords provided by Novartis:

HBeAg-positive, chronic hepatitis B
telbivudine
entecavir
viral kinetics

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections

Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012