Entecavir Plus Adefovir Combination Therapy Versus Entecavir Monotherapy vs Therapy With Adefovir Plus Lamivudine for Chronic Hepatitis B Infected Subjects With Lamivudine-resistant Virus

Condition(s) targeted: Hepatitis B, Chronic

Intervention: Entecavir (Drug); Tenofovir (Drug); Adefovir (Drug); Lamivudine (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Bristol-Myers Squibb

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

Overall contact:
For participation information at a USA site use a phone number below. For site information outside the USA please email:, Email: Clinical.Trials@bms.com

The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine

Official 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

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the comparator therapy groups who achieve HBV DNA <50 IU/mL (approximately 300 copies/mL)

Secondary outcome:

Proportion of subjects who achieve HBV DNA < the lower limit of quantitation (LLD LOQ) for the Roche COBAS® TaqMan -(LOQ = 29 IU/mL [approximately 169 copies/mL]

Proportion of subjects who achieve HBV DNA < the lower limit of detection (LOD) for the Roche COBAS® Taqman - (LOD = 10 IU/mL [approximately 58 copies/mL])

Proportions of subjects with HBV DNA in clinically relevant categories (eg HBV DNA values categorized in ranges that differ by 10 log increments)

Proportion of subjects with ALT > 1 x upper limit of normal (ULN) at baseline who achieve ALT normalization (<= 1 x ULN)

Descriptive rates of resistance in each treatment arm

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Evidence of lamivudine resistance

- Subjects must have a history of previous lamivudine 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 lamivudine

- Males or females ≥16 years of age (or minimum age of consent in a given country)

- Compensated liver function

- HBV DNA > 1. 72 x 10*4* (approximately 10*5* copies/mL)

- Documentation of HBeAg-positive and HBeAb-negative status at screening

- Males and females >=16 years of age (or minimum age of consent in a given country)

- 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:

- Amenorrhea >= 12 consecutive months without another cause

- For women with irregular menstrual periods and on hormone replacement therapy (HRT),

a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL

- 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 HCG) within 72 hours prior to the start of investigational product

Exclusion Criteria:

- Evidence of decompensated cirrhosis

- Coinfection with HIV, HCV, or HDV

- Laboratory values out of protocol-specified range

For participation information at a USA site use a phone number below. For site information outside the USA please email:, Email: Clinical.Trials@bms.com

Local Institution, Athens 11527, Greece; Active, not recruiting

Local Institution, Shatin 30-32, Hong Kong; Recruiting
Site 075

Local Institution, Kowloon -, Hong Kong; Not yet recruiting
Site 098

Local Institution, Tai Po ., Hong Kong; Not yet recruiting
Site 119

Local Institution, Hong Kong *, Hong Kong; Not yet recruiting
Site 134

Local Institution, Lucknow 226014, India; Recruiting
Site 001

Local Institution, New Delhi 110002, India; Recruiting
Site 002

Local Institution, Vellore 632004, India; Recruiting
Site 060

Local Institution, Ludhiana 141001, India; Terminated

Local Institution, Ahmedabad 380006, India; Recruiting
Site 121

Local Institution, Chandigarh 160012, India; Recruiting
Site 126

Local Institution, Indore 452014, India; Recruiting
Site 140

Local Institution, New Delhi 110062, India; Not yet recruiting
Site 141

Local Institution, Mumbai 400 008, India; Not yet recruiting
Site 142

Local Institution, Jakarta 10350, Indonesia; Recruiting
Site 097

Local Institution, Brescia 25123, Italy; Recruiting
Site 037

Local Institution, Antella Firenze 50012, Italy; Recruiting
Site 038

Local Institution, Roma 00149, Italy; Not yet recruiting
Site 068

Local Institution, Seoul 110-744, Korea, Republic of; Recruiting
Site 080

Local Institution, Seoul 152-703, Korea, Republic of; Recruiting
Site 081

Local Institution, Seoul 135-710, Korea, Republic of; Recruiting
Site 090

Local Institution, Seoul 120-752, Korea, Republic of; Recruiting
Site 091

Local Institution, Daegu 700-712, Korea, Republic of; Recruiting
Site 092

Local Institution, Pusan 602-739, Korea, Republic of; Recruiting
Site 093

Local Institution, Suwon 443-721, Korea, Republic of; Recruiting
Site 094

Local Institution, Seoul 138-736, Korea, Republic of; Recruiting
Site 095

Local Institution, Seoul 135-720, Korea, Republic of; Recruiting
Site 117

Local Institution, Seoul 136-705, Korea, Republic of; Recruiting
Site 123

Local Institution, Seoul 143-729, Korea, Republic of; Recruiting
Site 124

Local Institution, Seoul 156-755, Korea, Republic of; Recruiting
Site 125

Local Institution, Seoul 137-040, Korea, Republic of; Recruiting
Site 130

Local Institution, Pusan 626770, Korea, Republic of; Recruiting
Site 137

Local Institution, Bucheon 420767, Korea, Republic of; Recruiting
Site 139

Local Institution, Sungnam 463-712, Korea, Republic of; Recruiting
Site 143

Local Institution, Kuala Lumpur 50603, Malaysia; Recruiting
Site 076

Local Institution, Cebu City 6000, Philippines; Recruiting
Site 099

Local Institution, Manila 1502, Philippines; Recruiting
Site 120

Local Institution, Lodzi 91-347, Poland; Recruiting
Site 007

Local Institution, Kielce 25-317, Poland; Recruiting
Site 008

Local Institution, Warszawa 01-201, Poland; Recruiting
Site 010

Local Institution, Bialystok 15-540, Poland; Not yet recruiting
Site 013

Local Institution, Krakow 31-531, Poland; Recruiting
Site 016

Local Institution, Lublin 20-081, Poland; Recruiting
Site 017

Local Institution, Chorzow 41-500, Poland; Recruiting
Site 031

Local Institution, St. Petersburg 191163, Russian Federation; Not yet recruiting
Site 042

Local Institution, Moscow 115446, Russian Federation; Recruiting
Site 043

Local Institution, Moscow 117593, Russian Federation; Not yet recruiting
Site 044

Local Institution, St. Petersburg 191167, Russian Federation; Recruiting
Site 046

Local Institution, St. Petersburg 194044, Russian Federation; Not yet recruiting
Site 047

Local Institution, St. Petersburg 190103, Russian Federation; Recruiting
Site 048

Local Institution, Moscow 129110, Russian Federation; Recruiting
Site 049

Local Institution, Moscow 105275, Russian Federation; Recruiting
Site 050

Local Institution, Moscow 105275, Russian Federation; Recruiting
Site 056

Local Institution, St. Petersburg 191167, Russian Federation; Recruiting
Site 127

Local Institution, Singapore 119074, Singapore; Recruiting
Site 083

Local Institution, Taipei 100, Taiwan; Recruiting
Site 086

Local Institution, Tainan R.O.C. 70403, Taiwan; Recruiting
Site 087

Local Institution, Kaohsiung 80756, Taiwan; Recruiting
Site 088

Local Institution, Taoyuan 333, Taiwan; Recruiting
Site 118

Local Institution, Chiang Mai 50200, Thailand; Recruiting
Site 082

Local Institution, Bangkok 10160, Thailand; Recruiting
Site 084

Local Institution, Bornova Izmir 35100, Turkey; Recruiting
Site 034

Local Institution, Besevler Ankara 06620, Turkey; Not yet recruiting
Site 079

Local Institution, Trabzon 61080, Turkey; Recruiting
Site 089

Local Institution, Kayseri 38039, Turkey; Not yet recruiting
Site 104

Local Institution, Calgary, Alberta T2N 4N1, Canada; Recruiting
Site 108

Local Institution, Incheon, Amdong-Gu 405-760, Korea, Republic of; Not yet recruiting
Site 146

Local Institution, Vancouver, British Columbia V5Z 1H2, Canada; Recruiting
Site 107

University Of Connecticut Health Center, Farmington, Connecticut 06030, United States; Terminated

Local Institution, Seoul, Dongdaemun-Gu 130-702, Korea, Republic of; Recruiting
Site 133

Local Institution, Ulsan, Donggu 682-714, Korea, Republic of; Recruiting
Site 144

Local Institution, Chuncheon-Si, Gangwon-Do 200-704, Korea, Republic of; Not yet recruiting
Site 132

Local Institution, Wonju, Gangwon-Do 220-701, Korea, Republic of; Not yet recruiting
Site 145

Local Institution, Gangneung-Si, Gangwon-Do 210-711, Korea, Republic of; Not yet recruiting
Site 148

Local Institution, Ansan-Si, Gyeonggi-Do 425-707, Korea, Republic of; Recruiting
Site 129

Local Institution, Suwon-Si, Gyeonggi-Do 442-723, Korea, Republic of; Recruiting
Site 131

Local Institution, Anyang-Si, Gyeonggi-Do 431-070, Korea, Republic of; Not yet recruiting
Site 147

Local Institution, Goyang, Ilsanseo-Gu 414-410, Korea, Republic of; Recruiting
Site 138

Local Institution, Incheon, Jung-Gu 400-711, Korea, Republic of; Recruiting
Site 136

Local Institution, Concord, New South Wales 2139, Australia; Recruiting
Site 064

Local Institution, Seoul, Nowon-Gu 139872, Korea, Republic of; Recruiting
Site 135

Local Institution, Porto Alegre Rs, Rio Grande Do Sul 90035, Brazil; Completed

Local Institution, Kota Kinabalu, Sabah 88586, Malaysia; Recruiting
Site 110

Local Institution, Rosario, Santa Fe S2000KDS, Argentina; Recruiting
Site 122

Local Institution, Campinas, Sao Paulo 13083, Brazil; Recruiting
Site 077

BMS Clinical Trials Disclosure

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Starting date: March 2008
Ending date: May 2012
Last updated: September 22, 2009