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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00410202




Registration number
NCT00410202
Ethics application status
Date submitted
11/12/2006
Date registered
12/12/2006
Date last updated
21/11/2013

Titles & IDs
Public title
Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus
Scientific title
A Comparative Study of Entecavir vs. Adefovir Plus Lamivudine vs Combination Entecavir Plus Adefovir in Lamivudine-resistant Chronic Hepatitis B Subjects: The DEFINE Study
Secondary ID [1] 0 0
AI463-111
Universal Trial Number (UTN)
Trial acronym
DEFINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Entecavir
Treatment: Drugs - Tenofovir
Treatment: Drugs - Adefovir
Treatment: Drugs - Lamivudine

Active comparator: Entecavir - With the option of adding tenofovir at week 48. (This does not apply to Korea)

Active comparator: Adefovir + Lamivudine -

Active comparator: Entecavir + Adefovir -


Treatment: Drugs: Entecavir
Tablets, Oral, 1mg, once daily, 100 weeks

Treatment: Drugs: Tenofovir
Tablets, Oral, 300 mg, once daily

Treatment: Drugs: Adefovir
Tablets, Oral, 10mg, once daily, 100 weeks

Treatment: Drugs: Lamivudine
Tablets, Oral, 100mg, once daily, 100 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96
Timepoint [1] 0 0
Week 96
Secondary outcome [2] 0 0
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96
Timepoint [5] 0 0
Week 96
Secondary outcome [6] 0 0
Percentage of Participants With HBV DNA by PCR Category at Week 48
Timepoint [6] 0 0
Week 48
Secondary outcome [7] 0 0
Percentage of Participants With HBV DNA by PCR Category at Week 96
Timepoint [7] 0 0
Week 96
Secondary outcome [8] 0 0
Change in Mean log10 From Baseline in HBV DNA at Week 48
Timepoint [8] 0 0
Baseline, Week 48
Secondary outcome [9] 0 0
Change in Mean log10 From Baseline in HBV DNA at Week 96
Timepoint [9] 0 0
Baseline, Week 96
Secondary outcome [10] 0 0
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48
Timepoint [10] 0 0
Week 48
Secondary outcome [11] 0 0
Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96
Timepoint [11] 0 0
Baseline, Week 96
Secondary outcome [12] 0 0
Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)
Timepoint [13] 0 0
Week 96
Secondary outcome [14] 0 0
Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)
Timepoint [14] 0 0
Week 48
Secondary outcome [15] 0 0
Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)
Timepoint [15] 0 0
Week 96
Secondary outcome [16] 0 0
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Timepoint [16] 0 0
Week 48
Secondary outcome [17] 0 0
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96
Timepoint [17] 0 0
Week 96
Secondary outcome [18] 0 0
Percentage of Participants With HBsAg Seroconversion at Week 48
Timepoint [18] 0 0
Week 48
Secondary outcome [19] 0 0
Percentage of Participants With HBsAg Seroconversion at Week 96
Timepoint [19] 0 0
Week 96
Secondary outcome [20] 0 0
Cumulative Probability of Emergent Genotypic Resistance at Year 1
Timepoint [20] 0 0
Year 1
Secondary outcome [21] 0 0
Cumulative Probability of Emergent Genotypic Resistance at Year 2
Timepoint [21] 0 0
Year 2
Secondary outcome [22] 0 0
Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment
Timepoint [22] 0 0
From start of study therapy through Week 100 + 5 days
Secondary outcome [23] 0 0
Number of Participants With Laboratory Abnormalities: Hematology
Timepoint [23] 0 0
From start of study through Week 100 + 5 days
Secondary outcome [24] 0 0
Number of Participants With Laboratory Abnormalities: Serum Chemistry
Timepoint [24] 0 0
On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks

Eligibility
Key inclusion criteria
* Evidence of lamivudine (LVD) resistance
* Subjects must have a history of previous LVD treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S)
* Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV) infection
* Compensated liver function and must have met ALL of the following criteria:International normalization ratio (INR) = 1.5; Serum albumin = 3 g/dL (= 30 g/L); Serum total bilirubin = 2.5 mg/dL (= 42.75 µmol/L)
* HBV DNA > 1.72 x 10*4* IU/mL (approximately 10*5* copies/mL)
* Documentation of hepatitis B e antigen (HBeAg) positive and hepatitis B e antibody (HBeAb) negative status at screening
* alanine aminotransferase (ALT) = 10 * upper limit of normal (ULN) at screening
* Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized
* WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post menopausal is defined as:
* Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential
* WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the start of investigational product
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Evidence of decompensated cirrhosis
* Coinfection with human immunodeficiency virus, hepatitis C virus , or hepatitis D virus
* Women who are pregnant or breastfeeding
* Sexually active fertile men not using effective birth control if their partners were WOCBP
* Laboratory values out of protocol-specified range

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Local Institution - Concord
Recruitment hospital [2] 0 0
Local Institution - Randwick
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
Brazil
State/province [2] 0 0
Rio Grande Do Sul
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Greece
State/province [4] 0 0
Athens
Country [5] 0 0
Hong Kong
State/province [5] 0 0
New Territories
Country [6] 0 0
Hong Kong
State/province [6] 0 0
Hong Kong
Country [7] 0 0
Hong Kong
State/province [7] 0 0
Tai Po
Country [8] 0 0
India
State/province [8] 0 0
Uttar Pradesh
Country [9] 0 0
India
State/province [9] 0 0
Ahmedabad
Country [10] 0 0
India
State/province [10] 0 0
Chandigarh
Country [11] 0 0
India
State/province [11] 0 0
Indore
Country [12] 0 0
India
State/province [12] 0 0
Ludhiana
Country [13] 0 0
India
State/province [13] 0 0
New Delhi
Country [14] 0 0
India
State/province [14] 0 0
Vellore
Country [15] 0 0
Indonesia
State/province [15] 0 0
Jakarta
Country [16] 0 0
Italy
State/province [16] 0 0
Antella, Firenze
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Dongdaemun-Gu
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Donggu
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Gyeonggi-Do
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Ilsanseo Gu
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Jung-Gu
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Nowon-Gu
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Chuncheon-Si
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Daegu
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Gangneung
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Incheon
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Pusan
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Suwon
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Yangsan-Si
Country [31] 0 0
Malaysia
State/province [31] 0 0
Sabah
Country [32] 0 0
Malaysia
State/province [32] 0 0
Kuala Lumpur
Country [33] 0 0
Philippines
State/province [33] 0 0
Cebu City
Country [34] 0 0
Philippines
State/province [34] 0 0
Manila
Country [35] 0 0
Poland
State/province [35] 0 0
Chorzow
Country [36] 0 0
Poland
State/province [36] 0 0
Kielce
Country [37] 0 0
Poland
State/province [37] 0 0
Lodzi
Country [38] 0 0
Poland
State/province [38] 0 0
Lublin
Country [39] 0 0
Poland
State/province [39] 0 0
Warszawa
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Moscow
Country [41] 0 0
Russian Federation
State/province [41] 0 0
St. Petersburg
Country [42] 0 0
Singapore
State/province [42] 0 0
Singapore
Country [43] 0 0
Taiwan
State/province [43] 0 0
Kaohsiung
Country [44] 0 0
Taiwan
State/province [44] 0 0
Tainan R.O.C.
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taoyuan
Country [47] 0 0
Thailand
State/province [47] 0 0
Bangkok
Country [48] 0 0
Thailand
State/province [48] 0 0
Chiang Mai
Country [49] 0 0
Turkey
State/province [49] 0 0
Bornova Izmir
Country [50] 0 0
Turkey
State/province [50] 0 0
Trabzon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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

No documents have been uploaded by study researchers.