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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00412529
First received: December 15, 2006
Last updated: July 18, 2011
Last verified: July 2011

December 15, 2006
July 18, 2011
December 2006
February 2008   (final data collection date for primary outcome measure)
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.
Characterize the change in mean hepatitis B virus (HBV) DNA level from Baseline to Week 12 for telbivudine and entecavir.
Complete list of historical versions of study NCT00412529 on ClinicalTrials.gov Archive Site
  • 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.
  • • Change in mean HBV DNA level from Baseline to Weeks 2, 4, and 8
  • Characterization of very early viral kinetics through estimation of various parameters
  • Change in ALT (alanine aminotransferase) levels from Baseline to Week 12
  • The area under the curve (AUC) of HBV DNA change from Baseline to Week 12
  • % patients who are polymerase chain reaction (PCR) negative at Week 12
  • Safety assessed by adverse events and laboratory values
Not Provided
Not Provided
 
Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis B
  • Chronic Hepatitis B
  • Drug: Entecavir
    Entecavir 0.5 mg once daily for 12 weeks.
  • Drug: Telbivudine
    Telbivudine 600 mg once daily for 12 weeks.
  • Experimental: Telbivudine
    Intervention: Drug: Telbivudine
  • Active Comparator: Entecavir
    Intervention: Drug: Entecavir
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
Not Provided
February 2008   (final data collection date for primary outcome measure)

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

Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT00412529
CLDT600A2407
Not Provided
External Affairs, Novartis Pharmaceuticals
Novartis Pharmaceuticals
Merck Sharp & Dohme Corp.
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP