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Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB

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ClinicalTrials.gov Identifier: NCT00805675
Recruitment Status : Completed
First Posted : December 10, 2008
Results First Posted : February 28, 2012
Last Update Posted : February 28, 2012
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE December 9, 2008
First Posted Date  ICMJE December 10, 2008
Results First Submitted Date  ICMJE December 12, 2011
Results First Posted Date  ICMJE February 28, 2012
Last Update Posted Date February 28, 2012
Study Start Date  ICMJE November 2008
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12. [ Time Frame: Baseline, Week 12 ]
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2008)
The primary variable is the reduction of HBV DNA level over 12 weeks of treatment [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2012)
  • Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8. [ Time Frame: Baseline, Week 2, Week 4, Week 8 ]
    Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
  • Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12 [ Time Frame: Week 12 ]
    Polymerase Chain Reaction (PCR) Negative is defined as HBV DNA levels <25 copies/ml.
  • Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12 [ Time Frame: Week 12 ]
    HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). HBeAg stands for hepatitis B "e" antigen. This antigen is a protein from the hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the person is infectious and is able to spread the virus to other people.
  • Characterization of Very Early Viral Kinetics Through Estimated Viral Load [ Time Frame: Week 12 ]
    The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
  • Characterization of Very Early Viral Kinetics Through Viral Clearance [ Time Frame: Week 12 ]
    The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
  • Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss [ Time Frame: Week 12 ]
    The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
  • Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production. [ Time Frame: Week 12 ]
    The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t) I(t) (1 ) (T I(t))V(t) I(t) where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise allinfected and uninfected target cells, and δ the rate of infected cell loss
  • Characterization of Very Early Viral Kinetics Through Half-live of Free Virus [ Time Frame: Week 12 ]
    The underlying bi-phasic model of viral kinetics can be described as follows: V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2008)
  • Reduction in HBV DNA level [ Time Frame: From baseline to Weeks 2, 4 and 8 ]
  • Characterization of very early viral kinetics through estimation of various parameters [ Time Frame: Week 12 ]
  • % of patients who are PCR negative [ Time Frame: Week 12 ]
  • % of patients who achieve HBeAg loss and HBeAg seroconversion [ Time Frame: Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
Official Title  ICMJE A Randomized, Open-label, Controlled, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine 600 mg and Tenofovir Disproxil Fumarate 300 mg in Combination or Telbivudine 600 mg or Tenofovir Disproxil Fumarate 300 mg Monotherapy Given Over 12 Weeks on the Kinetics of Hepatitis B Virus DNA in Adults With HBeAg Positive Compensated CHB
Brief Summary The purpose of this study is to compare the safety, tolerability and effectiveness of 12 weeks of treatment with telbivudine 600 mg daily plus tenofovir DF 300 mg one daily (OD) taken together vs. tenofovir DF 300 mg once daily (QD) or vs telbivudine 600 mg monotherapy daily (QD). This is an open labeled, active controlled, viral kinetics study which means the subjects and study doctor will know what study drug subjects have been assigned. This study is open to male and female subjects, <40 years of age, who have been infected with HBV for at least 6 months and have not received oral treatment for HBV.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis B Virus
Intervention  ICMJE
  • Drug: Telbivudine
    600 mg monotherapy supplied in film-coated tablets.
  • Drug: Tenofovir
    Tenofovir disoproxil fumarate was supplied in 300 mg tablets
  • Drug: Telbivudine plus tenofovir
    Telbivudine 600 mg and Tenofovir 300 mg were purchased in commercial packs. Patients were instructed to take medication(s) orally every morning either with or without food.
Study Arms  ICMJE
  • Experimental: Telbivudine 600 mg monotherapy
    All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
    Intervention: Drug: Telbivudine
  • Active Comparator: Tenofovir disproxil fumarate 300 mg monotherapy
    All patients in this arm were randomized to receive Tenofovir disoproxil fumarate 300 mg(equivalent to tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
    Intervention: Drug: Tenofovir
  • Active Comparator: Telbivudine 600 mg and Tenofovir 300 mg
    All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD and Tenofovir (TDF) 300 mg (equivalent to Tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
    Intervention: Drug: Telbivudine plus tenofovir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 26, 2012)
83
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2008)
60
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Chronic HBV infection, defined as positive serum HBsAg for at least 6 months, or HBsAg positive > 3 months and negative for IgM anti-HBc and positive for IgG anti-HBc
  • Age < 40 years old
  • HBeAg positive
  • HBV DNA > or = to 10^7 copies/mL by Abbott real-time PCR
  • ALT < or = to 1 ULN
  • Willing and able to provide written informed consent
  • No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
  • Is willing and able to comply with the study drug regimen and all other study procedures and requirements
  • Is willing and able to provide written informed consent before any study assessment is perform

Exclusion Criteria:

  • Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 × ULN, PT > 1.2 × ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).
  • Received interferon (pegylated or not) therapy within 6 months of the screening visit
  • α-fetoprotein > 50 ng/mL
  • Evidence of hepatocellular carcinoma (HCC)
  • Co-infection with HCV (by serology), or HIV,
  • Significant renal, cardiovascular, pulmonary, or neurological disease.
  • Received solid organ or bone marrow transplantation.
  • Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.
  • Has proximal tubulopathy.
  • Use of other investigational drugs at the time of enrollment, or within 30 days
  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
  • Is pregnant or breastfeeding.
  • Is a women of child-bearing potential (WOCBP)unless post-menopausal or using one or more acceptable method of contraception.
  • Patient has any other concurrent medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study.
  • Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
  • Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir.

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00805675
Other Study ID Numbers  ICMJE CLDT600AHK01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date January 2012

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