Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B

NCT00410072 | Completed Phase 3 Results

• 1 other identifier: AI463-110
• Study Type: interventional
• Target: 669
• Locations: 13 countries
• Sites: 68

Brief Summary

The purpose of this study is to compare the effectiveness of entecavir plus tenofovir combination therapy with that of entecavir monotherapy. Safety will also be studied.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96

  HBV DNA levels \<50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.

  At Week 96

Secondary Outcomes (15)

• Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status

  At Weeks 48 and 96

• Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96

  At Weeks 48 and 96

• Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96

  At Weeks 48 and 96

• Mean Log 10 HBV DNA at Weeks 48 and 96

  Baseline, Weeks 48 and 96

• Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96

  At Weeks 48 and 96

Study Arms (2)

TDF 0.5 mg

EXPERIMENTAL

TDF=tenofovir

Drug: Entecavir

ETV 0.5 mg +TDF 300 mg

EXPERIMENTAL

ETV=entecavir; TDF=tenofovir

Drug: Entecavir + Tenofovir

Interventions

Entecavir DRUG

Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks

Also known as: Baraclude, BMS-200475

TDF 0.5 mg

Entecavir + Tenofovir DRUG

Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks

Also known as: Baraclude, BMS-200475

ETV 0.5 mg +TDF 300 mg

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:

• Chronic hepatitis B virus (HBV) infection (hepatitis B e antigen \[HbeAg\]-positive or negative) disease
• Nucleoside- and nucleotide-naive
• Males or females ≥16 years of age (or minimum age of consent in a given country)
• Compensated liver function
• HBV DNA \>1.72\*10\*5\*IU/mL (approximately 10\*6\*copies/mL) for HbeAg-positive participants
• HBV DNA \>1.72\*10\*4\*IU/mL (approximately 10\*5\*copies/mL) for Hbe-Ag-negative participants
• Alanine aminotransferase level ≥\*upper limit of normal (ULN) and ≤10\*ULN

You may not qualify if:

• Evidence of decompensated cirrhosis
• Coinfection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
• Laboratory values out of protocol-specified range

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (68)

Sergio E. Rojter

Los Angeles, California, 90017, United States

Location

Tuan Nguyen, Md

San Diego, California, 92105, United States

Location

San Jose Gastroenterology

San Jose, California, 95128, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06510, United States

Location

University Of Miami

Miami, Florida, 33136, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30308, United States

Location

Digestive Healthcare Of Georgia

Atlanta, Georgia, 30309, United States

Location

Digestive Disease Associates, P.A.

Baltimore, Maryland, 21229, United States

Location

Maryland Digestive Disease Research, Llc

Laurel, Maryland, 20707, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University Of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Sing Chan, Md

Flushing, New York, 11355, United States

Location

North Shore University

Manhasset, New York, 11030, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Concorde Medical Group

New York, New York, 10016, United States

Location

Mount Sinai School Of Medicine

New York, New York, 10029, United States

Location

Local Institution

Ciudad de Buenos Aires, Buenos Aires, C1121ABE, Argentina

Location

Local Institution

Ciudad de Buenos Aires, Buenos Aires, C1181ACH, Argentina

Location

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Ciudad de Buenos Aires, Buenos Aires, C1282AEN, Argentina

Location

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Rosario, Prov de Santa, S2000PBJ, Argentina

Location

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Westmead Nsw, New South Wales, 2145, Australia

Location

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Clayton Vic, Victoria, 3168, Australia

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Fitzroy, Victoria, 3065, Australia

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Heidelberg, Victoria, 3084, Australia

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Prahan, Victoria, 3004, Australia

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Belo Horizonte, Minas Gerais, 30150, Brazil

Location

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

Location

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Calgary, Alberta, T2N 4Z6, Canada

Location

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Vancouver, British Columbia, V5Z 1H2, Canada

Location

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Winnipeg, Manitoba, R3E 3P4, Canada

Location

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Toronto, Ontario, M3N 2V7, Canada

Location

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Toronto, Ontario, M5G 2N2, Canada

Location

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Toronto, Ontario, M5T 2S8, Canada

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Grenoble, 38043, France

Location

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Marseille, 13285, France

Location

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Paris, 75013, France

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Paris, 75014, France

Location

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Paris, 75571, France

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Strasbourg, 67090, France

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Hyderabad, Andhra Pradesh, 500082, India

Location

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Lucknow, 226014, India

Location

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Ludhiana, 141001, India

Location

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Vellore, 632004, India

Location

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Antella Firenze, 50012, Italy

Location

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Brescia, 25123, Italy

Location

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Pisa, 56124, Italy

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Roma, 00149, Italy

Location

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Durango, Durango, 34229, Mexico

Location

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Bialystok, 15-540, Poland

Location

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Chorzów, 41-500, Poland

Location

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Krakow, 31-531, Poland

Location

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Lublin, 20-081, Poland

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Warsaw, 01-201, Poland

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Moscow, 105275, Russia

Location

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Moscow, 115446, Russia

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Moscow, 117593, Russia

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Saint Petersburg, 190103, Russia

Location

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Saint Petersburg, 191163, Russia

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Saint Petersburg, 191167, Russia

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Saint Petersburg, 194044, Russia

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Smolensk, 214018, Russia

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Pretoria, Gauteng, 0001, South Africa

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Bellville, Western Cape, 7530, South Africa

Location

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N1 City Goodwood, Western Cape, 7463, South Africa

Location

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Bornova Izmir, 35100, Turkey (Türkiye)

Location

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Cebeci Ankara, 06620, Turkey (Türkiye)

Location

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Sihhiye Ankara, 06100, Turkey (Türkiye)

Location

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Trabzon, 61080, Turkey (Türkiye)

Location

Related Publications (1)

• Lok AS, Trinh H, Carosi G, Akarca US, Gadano A, Habersetzer F, Sievert W, Wong D, Lovegren M, Cohen D, Llamoso C. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naive patients with chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):619-628.e1. doi: 10.1053/j.gastro.2012.05.037. Epub 2012 May 27.

  PMID: 22643350 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; Tenofovir

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

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: April 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: March 15, 2013
• Results First Posted: February 3, 2012

Record last verified: 2013-03

Locations

IT (4); ME (1); RU (8); TU (4); AU (5); ZA (3); AR (4); CA (6); IN (4); BR (2); PL (5); US (16); FR (6)