Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00737568
Registration number
NCT00737568
Ethics application status
Date submitted
15/08/2008
Date registered
19/08/2008
Date last updated
11/03/2016
Titles & IDs
Public title
Tenofovir Disoproxil Fumarate (Tenofovir DF) Versus Emtricitabine/Tenofovir DF in Subjects Resistant to Lamivudine
Query!
Scientific title
A Phase 3b, Randomized, Double-Blind, Double-Dummy Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects With Chronic Hepatitis B Who Are Resistant to Lamivudine
Query!
Secondary ID [1]
0
0
GS-US-174-0121
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Hepatitis B
0
0
Query!
Condition category
Condition code
Infection
0
0
0
0
Query!
Other infectious diseases
Query!
Oral and Gastrointestinal
0
0
0
0
Query!
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - TDF
Treatment: Drugs - FTC/TDF
Treatment: Drugs - TDF Placebo
Treatment: Drugs - FTC/TDF Placebo
Experimental: Tenofovir DF - TDF plus placebo to match FTC/TDF
Experimental: FTC/TDF - FTC/TDF plus placebo to match TDF
Treatment: Drugs: TDF
Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablet administered orally once daily
Treatment: Drugs: FTC/TDF
Emtricitabine (FTC)/TDF 200/300 mg fixed-dose combination tablet administered orally once daily
Treatment: Drugs: TDF Placebo
TDF placebo tablet administered orally once daily
Treatment: Drugs: FTC/TDF Placebo
FTC/TDF placebo tablet administered orally once daily
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Week 96
Query!
Secondary outcome [1]
0
0
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Weeks 48, 144, 192, and 240
Query!
Secondary outcome [2]
0
0
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [3]
0
0
HBV DNA Level at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [4]
0
0
Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [4]
0
0
Normal ALT was defined as having a value less than or equal to the ULN. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged = 69.
Query!
Timepoint [4]
0
0
Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [5]
0
0
Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [5]
0
0
The percentage of participants who were HBeAg positive at baseline and who had HBeAg Loss at the given time point was summarized. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.
Query!
Timepoint [5]
0
0
Baseline; Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [6]
0
0
Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [6]
0
0
The percentage of participants who were HBeAg positive at baseline and who had seroconversion to anti-HBe at the given time point was summarized. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.
Query!
Timepoint [6]
0
0
Baseline; Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [7]
0
0
Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [7]
0
0
The percentage of participants with HBsAg Loss at the given time point was summarized. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.
Query!
Timepoint [7]
0
0
Baseline; Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [8]
0
0
Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [8]
0
0
The percentage of participants with seroconversion to anti-HBs at the given time point was summarized. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.
Query!
Timepoint [8]
0
0
Baseline; Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [9]
0
0
Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240
Query!
Assessment method [9]
0
0
The percentage of participants with virologic breakthrough at the given time point was summarized. Virologic breakthrough was defined as having two consecutive 1.0 log10 or greater increases in serum HBV DNA from on-treatment nadir, or two consecutive HBV DNA values = 400 copies/mL after being \< 400 copies/mL.
Query!
Timepoint [9]
0
0
Baseline; Weeks 48, 96, 144, 192, and 240
Query!
Secondary outcome [10]
0
0
Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240
Query!
Assessment method [10]
0
0
BMD is calculated as grams per cubic centimeter (g/cm\^2); the mean (SD) percentage change is presented.
Query!
Timepoint [10]
0
0
Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240
Query!
Secondary outcome [11]
0
0
Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240
Query!
Assessment method [11]
0
0
BMD is calculated as g/cm\^2; the mean (SD) percentage change is presented.
Query!
Timepoint [11]
0
0
Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240
Query!
Secondary outcome [12]
0
0
Development of Drug-resistant Mutations (DRMs)
Query!
Assessment method [12]
0
0
The development of DRMs was summarized, either as development of new DRMs or enrichment of existing DRMs.
Query!
Timepoint [12]
0
0
Baseline to Week 240
Query!
Eligibility
Key inclusion criteria
Inclusion Criteria
* Chronic HBV infection, defined as positive serum HBsAg for at least 6 months
* 18 through 75 years of age, inclusive
* HBV DNA = 10^3 IU/mL
* Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase mutation(s) known to confer resistance to lamivudine (rtM204I/V with or without rtL180M) by central laboratory assessment prior to randomization; adefovir dipivoxil treatment of = 48 weeks at the time of screening (inclusive of combination adefovir dipivoxil + lamivudine at entry) was allowed
* Willing and able to provide written informed consent
* Negative serum pregnancy test (for females of childbearing potential only)
* Calculated creatinine clearance = 50 mL/min
* Hemoglobin = 10 g/dL
* Neutrophils = 1000 /mm^3
* No prior oral HBV therapy with approved nucleotide and/or nucleoside therapy or other investigational agents for HBV infection other than lamivudine or adefovir dipivoxil
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
75
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Exclusion Criteria
* Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
* Males and females of reproductive potential who are not willing to use an effective method of contraception during the study
* Alanine aminotransferase (ALT) = 10 × the upper limit of the normal range (ULN)
* Decompensated liver disease
* Interferon or pegylated interferon therapy within 6 months of the screening visit
* Alpha fetoprotein > 50 ng/mL
* Evidence of hepatocellular carcinoma
* Coinfection with hepatitis C virus, HIV, or hepatitis D virus
* Significant renal, cardiovascular, pulmonary, or neurological disease
* Received solid organ or bone marrow transplantation
* Receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
* Proximal tubulopathy
* Known hypersensitivity to the study drugs, the metabolites or formulation excipients
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/09/2008
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/02/2015
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
280
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Florida
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
New York
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Pennsylvania
Query!
Country [4]
0
0
Austria
Query!
State/province [4]
0
0
Innsbruck
Query!
Country [5]
0
0
Austria
Query!
State/province [5]
0
0
Wien
Query!
Country [6]
0
0
Bulgaria
Query!
State/province [6]
0
0
Sofia
Query!
Country [7]
0
0
Bulgaria
Query!
State/province [7]
0
0
Varna
Query!
Country [8]
0
0
Canada
Query!
State/province [8]
0
0
British Columbia
Query!
Country [9]
0
0
Canada
Query!
State/province [9]
0
0
Manitoba
Query!
Country [10]
0
0
Canada
Query!
State/province [10]
0
0
Ontario
Query!
Country [11]
0
0
Czech Republic
Query!
State/province [11]
0
0
Brno
Query!
Country [12]
0
0
Czech Republic
Query!
State/province [12]
0
0
Plzen
Query!
Country [13]
0
0
Czech Republic
Query!
State/province [13]
0
0
Prague
Query!
Country [14]
0
0
Czech Republic
Query!
State/province [14]
0
0
Praha 4
Query!
Country [15]
0
0
Czech Republic
Query!
State/province [15]
0
0
Usti Nad Labem
Query!
Country [16]
0
0
Germany
Query!
State/province [16]
0
0
Baden-Wuerttemberg
Query!
Country [17]
0
0
Germany
Query!
State/province [17]
0
0
Berlin
Query!
Country [18]
0
0
Germany
Query!
State/province [18]
0
0
Duesseldorf
Query!
Country [19]
0
0
Germany
Query!
State/province [19]
0
0
Essen
Query!
Country [20]
0
0
Germany
Query!
State/province [20]
0
0
Frankfurt
Query!
Country [21]
0
0
Germany
Query!
State/province [21]
0
0
Hamburg
Query!
Country [22]
0
0
Germany
Query!
State/province [22]
0
0
Hannover
Query!
Country [23]
0
0
Germany
Query!
State/province [23]
0
0
Stuttgart
Query!
Country [24]
0
0
Greece
Query!
State/province [24]
0
0
Larissa
Query!
Country [25]
0
0
Greece
Query!
State/province [25]
0
0
Patras
Query!
Country [26]
0
0
Greece
Query!
State/province [26]
0
0
Thessaloniki
Query!
Country [27]
0
0
Hungary
Query!
State/province [27]
0
0
Budapest
Query!
Country [28]
0
0
Hungary
Query!
State/province [28]
0
0
Debrecen
Query!
Country [29]
0
0
Hungary
Query!
State/province [29]
0
0
Gyula
Query!
Country [30]
0
0
Hungary
Query!
State/province [30]
0
0
Kasposvar
Query!
Country [31]
0
0
New Zealand
Query!
State/province [31]
0
0
Auckland
Query!
Country [32]
0
0
New Zealand
Query!
State/province [32]
0
0
Hamilton
Query!
Country [33]
0
0
New Zealand
Query!
State/province [33]
0
0
Wellington
Query!
Country [34]
0
0
Poland
Query!
State/province [34]
0
0
Bialystok
Query!
Country [35]
0
0
Poland
Query!
State/province [35]
0
0
Bydgoszcz
Query!
Country [36]
0
0
Poland
Query!
State/province [36]
0
0
Chorzow
Query!
Country [37]
0
0
Poland
Query!
State/province [37]
0
0
Krakow
Query!
Country [38]
0
0
Poland
Query!
State/province [38]
0
0
Lodz
Query!
Country [39]
0
0
Poland
Query!
State/province [39]
0
0
Szczecin
Query!
Country [40]
0
0
Poland
Query!
State/province [40]
0
0
Warszawa
Query!
Country [41]
0
0
Poland
Query!
State/province [41]
0
0
Wroclaw
Query!
Country [42]
0
0
Romania
Query!
State/province [42]
0
0
Judetul lasi
Query!
Country [43]
0
0
Romania
Query!
State/province [43]
0
0
Judetul Timis
Query!
Country [44]
0
0
Romania
Query!
State/province [44]
0
0
Bucharest
Query!
Country [45]
0
0
Romania
Query!
State/province [45]
0
0
Bucuresti
Query!
Country [46]
0
0
Romania
Query!
State/province [46]
0
0
Cluj-Napoca
Query!
Country [47]
0
0
Romania
Query!
State/province [47]
0
0
Constanta
Query!
Country [48]
0
0
Serbia
Query!
State/province [48]
0
0
Belgrade
Query!
Country [49]
0
0
Serbia
Query!
State/province [49]
0
0
Kragujevac
Query!
Country [50]
0
0
Serbia
Query!
State/province [50]
0
0
Nis
Query!
Country [51]
0
0
Serbia
Query!
State/province [51]
0
0
Novi Sad
Query!
Country [52]
0
0
Spain
Query!
State/province [52]
0
0
Sevilla
Query!
Country [53]
0
0
Turkey
Query!
State/province [53]
0
0
Ankara
Query!
Country [54]
0
0
Turkey
Query!
State/province [54]
0
0
Bursa
Query!
Country [55]
0
0
Turkey
Query!
State/province [55]
0
0
Izmir
Query!
Country [56]
0
0
Turkey
Query!
State/province [56]
0
0
Samsun
Query!
Country [57]
0
0
Turkey
Query!
State/province [57]
0
0
Trabzon
Query!
Country [58]
0
0
Turkey
Query!
State/province [58]
0
0
Uskudar
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Gilead Sciences
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain suppression of viral replication to prevent the emergence of complications, which requires long-term therapy. Durable suppression of viral replication is achieved in the treatment of chronic viral diseases by preventing of the emergence of drug-resistant mutations. The clinical guidelines for the management of lamivudine resistant patients are variable. Some recommend switching to another agent without cross-resistance, while others recommend adding on another agent without cross-resistance. Limited clinical data exists to demonstrate whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for lamivudine resistant patients or if it should be used as part of a combination therapy regimen. This study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or without the rtL180M mutation) over a 240-week period. Participants in this study must be receiving lamivudine treatment at the time of enrollment.
Query!
Trial website
https://clinicaltrials.gov/study/NCT00737568
Query!
Trial related presentations / publications
Corsa AC, Liu Y, Flaherty JF, Mitchell B, Fung SK, Gane E, Miller MD, Kitrinos KM. No resistance to tenofovir disoproxil fumarate through 96 weeks of treatment in patients with lamivudine-resistant chronic hepatitis B. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2106-12.e1. doi: 10.1016/j.cgh.2014.05.024. Epub 2014 Jun 11. Liu Y, Fung S, Gane EJ, Dinh P, Flaherty JF, Svarovskaia ES, Miller MD, Kitrinos KM. Evaluation of HBV DNA decay kinetics in patients containing both rtM204V/I mutant and wild-type HBV subpopulations during tenofovir DF (TDF) monotherapy or combination therapy with emtricitabine (FTC)/TDF. J Med Virol. 2014 Sep;86(9):1473-81. doi: 10.1002/jmv.23982. Epub 2014 May 23. Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, Gurel S, Caruntu FA, Flaherty JF, Massetto B, Dinh P, Corsa A, Subramanian GM, McHutchison JG, Husa P, Gane E. Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2014 Apr;146(4):980-8. doi: 10.1053/j.gastro.2013.12.028. Epub 2013 Dec 22. Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, Gurel S, Caruntu FA, Flaherty JF, Massetto B, Kim K, Kitrinos KM, Subramanian GM, McHutchison JG, Yee LJ, Elkhashab M, Berg T, Sporea I, Yurdaydin C, Husa P, Jablkowski MS, Gane E. Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study. J Hepatol. 2017 Jan;66(1):11-18. doi: 10.1016/j.jhep.2016.08.008. Epub 2016 Aug 18.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
John Flaherty, PharmD
Query!
Address
0
0
Gilead Sciences
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Type
Citations or Other Details
Journal
Corsa AC, Liu Y, Flaherty JF, Mitchell B, Fung SK,...
[
More Details
]
Journal
Liu Y, Fung S, Gane EJ, Dinh P, Flaherty JF, Svaro...
[
More Details
]
Journal
Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann...
[
More Details
]
Results are available at
https://clinicaltrials.gov/study/NCT00737568
Download to PDF