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

NCT00410202 | Completed Phase 3 Results

• 1 other identifier: AI463-111
• Study Type: interventional
• Target: 629
• Locations: 18 countries
• Sites: 67

Brief Summary

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

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• 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

  HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (\<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA \<50 IU/mL; N = number of participants analyzed.

  Week 48

Secondary Outcomes (24)

• Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96

  Week 96

• Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48

  Week 48

• Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96

  Week 96

• Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48

  Week 48

• Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96

  Week 96

Study Arms (3)

Entecavir

ACTIVE COMPARATOR

With the option of adding tenofovir at week 48. (This does not apply to Korea)

Drug: Entecavir; Drug: Tenofovir

Adefovir + Lamivudine

ACTIVE COMPARATOR

Drug: Adefovir; Drug: Lamivudine

Entecavir + Adefovir

ACTIVE COMPARATOR

Drug: Entecavir; Drug: Adefovir

Interventions

Entecavir DRUG

Tablets, Oral, 1mg, once daily, 100 weeks

Also known as: Baraclude, BMS-200475

Entecavir; Entecavir + Adefovir

Tenofovir DRUG

Tablets, Oral, 300 mg, once daily

Also known as: Viread

Entecavir

Adefovir DRUG

Tablets, Oral, 10mg, once daily, 100 weeks

Also known as: Hepsera

Adefovir + Lamivudine; Entecavir + Adefovir

Lamivudine DRUG

Tablets, Oral, 100mg, once daily, 100 weeks

Also known as: Epivir

Adefovir + Lamivudine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (67)

University Of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Local Institution

Concord, New South Wales, 2139, Australia

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Randwick, New South Wales, 2031, Australia

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Porto Alegre Rs, Rio Grande do Sul, 90035, Brazil

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Calgary, Alberta, T2N 4N1, Canada

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Athens, 11527, Greece

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Hong Kong, Hong Kong, Hong Kong

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Shatin, New Territories, Hong Kong

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Tai Po, Hong Kong

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Lucknow, Uttar Pradesh, 226014, India

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Ahmedabad, 380006, India

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Chandigarh, 160012, India

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Indore, 452014, India

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Ludhiana, 141001, India

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New Delhi, 110002, India

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Vellore, 632004, India

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Jakarta, 10350, Indonesia

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Antella, Firenze, 50012, Italy

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Kota Kinabalu, Sabah, 88586, Malaysia

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Kuala Lumpur, 50603, Malaysia

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Cebu City, 6000, Philippines

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Manila, 1502, Philippines

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Chorzów, 41-500, Poland

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Kielce, 25-317, Poland

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Lodz, 91-347, Poland

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Lublin, 20-081, Poland

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Warsaw, 01-201, Poland

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Moscow, 105275, Russia

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Moscow, 115446, Russia

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Saint Petersburg, 190103, Russia

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Saint Petersburg, 191167, Russia

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Singapore, 119074, Singapore

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Seoul, Dongdaemun-Gu, 130-702, South Korea

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Ulsan, Donggu, 682-714, South Korea

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Ansan-si, Gyeonggi-do, 425-707, South Korea

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Anyang-si, Gyeonggi-do, 431-070, South Korea

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Bucheon-si, Gyeonggi-do, 420767, South Korea

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Seongnam-si, Gyeonggi-do, 463 712, South Korea

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Suwon, Gyeonggi-do, 442-723, South Korea

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Koyang, Ilsanseo Gu, 411-706, South Korea

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Incheon, Jung-Gu, 400-711, South Korea

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Seoul, Nowon-Gu, 139-872, South Korea

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Chuncheon, 200-704, South Korea

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Daegu, 700-721, South Korea

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Gangneung, 210-711, South Korea

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Incheon, 405-760, South Korea

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Pusan, 602-739, South Korea

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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Seoul, 135-710, South Korea

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Seoul, 135-720, South Korea

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Seoul, 136-705, South Korea

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Seoul, 137-040, South Korea

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Seoul, 138-736, South Korea

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Seoul, 143-729, South Korea

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Seoul, 152-703, South Korea

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Seoul, 156-755, South Korea

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Suwon, 443-721, South Korea

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Yangsan, 626770, South Korea

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Kaohsiung City, 80756, Taiwan

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Tainan R.o.c., 70403, Taiwan

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Taipei, 100, Taiwan

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Taoyuan District, 333, Taiwan

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Bornova Izmir, 35100, Turkey (Türkiye)

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Trabzon, 610808, Turkey (Türkiye)

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; Tenofovir; adefovir; adefovir dipivoxil; Lamivudine

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 12, 2006
• Study Start: March 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: July 1, 2012
• Last Updated: November 21, 2013
• Results First Posted: July 4, 2012

Record last verified: 2013-10

Locations

PL (5); TH (2); KR (27); ID (1); IT (1); PH (2); BR (1); US (1); AU (2); SG (1); TW (4); RU (4); GR (1); MY (2); CA (1); IN (7); HK (3); TU (2)