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); Adefovir + Lamivudine (Drug); Entecavir + Adefovir (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: To compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the monotherapy groups who achieve HBV DNA <50 IU/mL (approximately 300 copies/mL)

Secondary outcome:

To compare the proportion of subjects in the combination therapy group to the proportion of subjects in each of the monotherapy groups who achieve HBV DNA <50 IU/mL (approximately 300 copies/mL)

Mean Log10 reduction from baseline in HBV DNA

ALT normalization (≤ 1 x upper limit of normal)

HBeAg loss

HBe seroconversion

HBs seroconversion

Virologic rebound due to genotypic resistance

Frequency of adverse events, serious adverse events, and discontinuations from study drug due to adverse events or laboratory abnormalities

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

Criteria:

Inclusion Criteria:

- Evidence of lamivudine resistance

- Chronic HBV infection with HbeAg-positive disease

- 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)

- ALT ≤10 x upper limit of normal

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; Not yet recruiting
Site 111

Local Institution, Athens 11522, Greece; Not yet recruiting
Site 112

Local Institution, Shatin 30-32, Hong Kong; Not yet 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, Lucknow 226014, India; Recruiting
Site 001

Local Institution, New Delhi 110002, India; Not yet recruiting
Site 002

Local Institution, Vellore 632004, India; Recruiting
Site 060

Local Institution, Ludhiana 141001, India; Recruiting
Site 065

Local Institution, Ahmedabad 380006, India; Recruiting
Site 121

Local Institution, Jakarta 10350, Indonesia; Not yet recruiting
Site 097

Local Institution, Denpasar, Bali 80114, Indonesia; Not yet recruiting
Site 115

Local Institution, Brescia 25123, Italy; Not yet recruiting
Site 037

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

Local Institution, Roma 00149, Italy; 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; Not yet recruiting
Site 123

Local Institution, Seoul 143-729, Korea, Republic of; Not yet recruiting
Site 124

Local Institution, Seoul 156-755, Korea, Republic of; Not yet recruiting
Site 125

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

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

Local Institution, Manila 1502, Philippines; Not yet 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; Recruiting
Site 013

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

Local Institution, Lublin 20-089, Poland; Recruiting
Site 017

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

Local Institution, St. Petersburg 191163, Russian Federation; Recruiting
Site 042

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

Local Institution, Moscow 117593, Russian Federation; Recruiting
Site 044

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

Local Institution, St. Petersburg 194044, Russian Federation; Recruiting
Site 047

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

Local Institution, Moscow 129110, Russian Federation; Not yet recruiting
Site 049

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

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

Local Institution, Singapore 119074, Singapore; Recruiting
Site 083

Local Institution, Taipei 100, Taiwan; Recruiting
Site 086

Local Institution, Tainan R.O.C. 70403, Taiwan; Not yet recruiting
Site 087

Local Institution, Kaohsiung 80756, Taiwan; Recruiting
Site 088

Local Institution, Taoyuan 333, Taiwan; Not yet 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, Sihhiye Ankara 06100, Turkey; Not yet recruiting
Site 035

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

Local Institution, Trabzon 61080, Turkey; Not yet recruiting
Site 089

Local Institution, Gorukle Bursa 16059, Turkey; Not yet recruiting
Site 101

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

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

Local Institution, Vancouver, British Columbia V5Z 1H2, Canada; Not yet recruiting
Site 107

Sergio E. Rojter, M.D., Los Angeles, California 90017, United States; Recruiting
Sergio E. Rojter, Site 100

Yale University School Of Medicine, New Haven, Connecticut 06520, United States; Recruiting
Joseph Lim, Site 054

Local Institution, Farmington, Connecticut 06030, United States; Not yet recruiting
Site 055

Local Institution, Mumbai, Maharashtra 400020, India; Not yet recruiting
Site 109

Coleman Smith, Md, Plymouth, Massachusetts 55446, United States; Recruiting
Coleman Smith, Site 078

Local Institution, Randwick, New South Wales 2031, Australia; Recruiting
Site 063

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

Local Institution, Kogarah Nsw, New South Wales 2217, Australia; Recruiting
Site 074

Concorde Medical Group, New York, New York 10016, United States; Recruiting
Hillel Tobias, Site 113

Local Institution, Woolloongabba, Queensland 4102, Australia; Recruiting
Site 070

Local Institution, Porto Alegre Rs, Rio Grande Do Sul 90035, Brazil; Not yet recruiting
Site 059

Local Institution, Kota Kinabalu, Sabah 88586, Malaysia; Not yet recruiting
Site 110

Local Institution, Rosario, Santa Fe S2000KDS, Argentina; Not yet recruiting
Site 122

Local Institution, Campinas, Sao Paulo 13083, Brazil; Not yet recruiting
Site 077

Local Institution, Clayton Vic, Victoria 3168, Australia; Recruiting
Site 062

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: February 2012
Last updated: October 20, 2008