Suboptimal Responders to Adefovir Switching to Entecavir

NCT00718887 | Completed Phase 4 Results

• 1 other identifier: AI463-171
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 8

Brief Summary

Switching to Entecavir will result in superior antiviral efficacy as compared to continuing with Adefovir in patients with a suboptimal response to Adefovir

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing

  HBV DNA Level \<50 IU/mL=approximately 300 copies/mL.

  At Week 12 from Day 1

Secondary Outcomes (8)

• Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing

  At Week 48 from Day 1

• Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing

  At Weeks 12 and 48 from Day 1

• Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)

  At Weeks 12 and 48 from Day 1

• Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion

  At Weeks 12 and 48 from Day 1

• Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion

  At Weeks 12 and 48 from Day 1

Study Arms (2)

Entecavir, 0.5 mg QD

EXPERIMENTAL

Drug: Entecavir

Adefovir, 10 mg QD/Entecavir, 0.5 mg QD

OTHER

Control

Drug: Adefovir/Entecavir

Interventions

Entecavir DRUG

Tablets, Oral, 0.5 mg, once daily (QD), 52 weeks

Also known as: Baraclude, BMS-200475

Entecavir, 0.5 mg QD

Adefovir/Entecavir DRUG

Tablets, Oral, 10-mg adefovir QD for 12 weeks followed by 0.5-mg entecavir QD for a maximum of 52 weeks

Also known as: Baraclude, BMS-200475

Adefovir, 10 mg QD/Entecavir, 0.5 mg QD

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 infection with hepatitis B virus (HBV)(detectable hepatitis B surface antibody (HBsAg) at screening and at least 24 weeks prior to screening, or detectable HBsAg for \<24 weeks and negative for immunoglobulin M core antibody)
• Documentation of hepatitis B e antigen (HBeAg) positive or negative status
• Naive to nucleoside/nucleotide analogues, with the exception of adefovir
• Suboptimal response to adefovir treatment
• No lamivudine/telbivudine, entecavir, or adefovir resistance-associated substitutions at screening
• Male or female gender, aged 16 years and older
• Compensated liver function
• Serum alanine aminotransferase level \<10\*upper limit of normal at screening

You may not qualify if:

• Women who are pregnant or breastfeeding
• Evidence of decompensated cirrhosis
• Coinfection with HIV, hepatitis C virus, or hepatitis D virus
• Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication)
• Chronic renal insufficiency, defined as a creatinine clearance \<50 mL/min
• Current abuse of illegal drugs or alcohol, sufficient in the investigator's opinion to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis
• Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications
• Serum creatinine level \>1.5 mg/dL; hemoglobin level \<10.0 g/dL; platelet count \<70,000/mm\^3; absolute neutrophil count \<1500 cells/mm\^3; serum alpha fetoprotein level \>100 ng/mL
• Except adefovir, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (eg, lamivudine, entecavir), or any other experimental anti-HBV antiviral, or any China Traditional Medicine
• Therapy with interferon, thymosin alpha, or other immunostimulators within 24 weeks of randomization
• Required chronic administration of medications that cause immunosuppression, that are associated with a high risk of nephrotoxicity or hepatotoxicity, or that affect renal excretion.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (8)

Local Institution

Beijing, Beijing Municipality, 100011, China

Location

Local Institution

Guiyang, Guizhou, 550004, China

Location

Local Institution

Nanjing, Jiangsu, 210002, China

Location

Local Institution

Nanchang, Jiangxi, 330006, China

Location

Local Institution

Changchun, Jilin, 130021, China

Location

Local Institution

Shenyang, Liaoning, 110004, China

Location

Local Institution

Shanghai, Shanghai Municipality, 200235, China

Location

Local Institution

Shanghai, Shanghai Municipality, China

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; adefovir

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

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 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2008
• First Posted: July 21, 2008
• Study Start: July 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2011
• Last Updated: February 11, 2013
• Results First Posted: February 11, 2013

Record last verified: 2013-01

Locations

CN (8)