Phase 3 N=191 Randomized Treatment

Comparison of Entecavir to Adefovir in Chronic Hepatitis B Virus (HBV) Patients With Hepatic Decompensation

Hepatitis B

Bottom Line

View on ClinicalTrials.gov: NCT00065507 ↗

Enrolled (actual)

191

Serious AEs

67.5%

Results posted

Jul 2010

Primary outcome: Primary: Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24 — -4.48; -3.40 log10 copies/mL — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Entecavir (ETV) (Drug); Adefovir (ADV) (Drug)
Age: Pediatric, Adult, Older Adult · 16+ yrs
Sex: All
Sponsor: Bristol-Myers Squibb
Primary completion: Oct 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Hepatitis B Virus (HBV) DNA by Polymerase Chain Reaction (PCR) at Week 24	-4.48; -3.40	<0.0001 sig
SECONDARY Change From Baseline in HBV DNA by PCR at Week 48	-4.66; -3.90	<0.0001 sig
SECONDARY Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 24	49; 15	<0.0001 sig
SECONDARY Number of Participants With HBV DNA < 300 Copies/mL by PCR At Week 48	57; 18	<0.0001 sig
SECONDARY Number of Participants Achieving Alanine Transaminase (ALT) Normalization (≤1.0 x Upper Limit of Normal [ULN]) at Weeks 24 and 48	46; 28; 49; 33	0.0193 sig
SECONDARY Number of Subjects Achieving Composite Endpoint (HBV DNA < 10*4 Copies/mL by PCR Assay and Normal ALT [≤ 1.0 x ULN]) Through Week 48	3; 1; 23; 6; 34; 11	—
SECONDARY >=2-Point Reduction From Baseline in Child-Pugh Score Through Week 48	0; 0; 14; 11; 23; 10	—
SECONDARY Number of Participants With Improvement or No Worsening in Child-Pugh Score From Baseline to Week 48	0; 0; 66; 67; 67; 62	—
SECONDARY Change From Baseline in Child-Pugh Score Through Week 48	8.8; 8.4; -0.4; -0.3; -0.4; -0.3	—
SECONDARY Number of Participants With Improvement in Child-Pugh Class at Week 24 and Week 48	25; 22; 35; 29	—
SECONDARY Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores From Baseline Through Week 48	17.1; 15.3; -0.1; 0.1; -0.8; -0.4	0.51
SECONDARY Improvement or No Worsening in MELD Score Through Week 48	0; 0; 58; 51; 63; 52	—
SECONDARY Mean Changes From Baseline in Quality of Life as Measured by the Short Form 36 (SF-36)	—	—
SECONDARY Mean Changes From Baseline in Quality of Life, as Measured by EuroQol-5D (EQ-5D) at Weeks 24 and 48	—	—
SECONDARY Change From Baseline in Albumin Through Week 48	3.00; 3.10; -0.04; -0.01; 0.01; -0.03	—
SECONDARY Mean Change From Baseline in Prothrombin Time Through Week 48	16.28; 15.35; -0.08; 0.03; -0.10; 0.06	—
SECONDARY Mean Change From Baseline in Total Bilirubin Through Week 48	2.80; 2.50; -0.06; 0.21; 0.11; -0.17	—
SECONDARY Change From Baseline in Platelet Count Through Week 48	87.32; 93.31; -0.93; -2.14; 3.55; 3.88	—
SECONDARY Participants Achieving Albumin Normalization Through Week 48	0; 0; 2; 7; 9; 6	—
SECONDARY Participants Achieving Prothrombin Time Normalization Through Week 48	0; 0; 3; 4; 5; 4	—
SECONDARY Participants Achieving Total Bilirubin Normalization Through Week 48	0; 0; 4; 9; 10; 9	—
SECONDARY Participants Achieving Platelet Count Normalization Through Week 48	0; 0; 3; 4; 3; 5	—
SECONDARY Number of Hepatocellular Carcinoma (HCC) Events at Different Time Points Through Week 48	2; 3; 5; 5; 10; 6	0.20
SECONDARY Cumulative Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, HCC, Discontinuations Due to AEs, and Confirmed Creatinine Increase >=0.5 mg/dL	91; 86; 55; 42; 70; 59	—
SECONDARY Number of Participants With Treatment-Emergent Grade 3/4 Laboratory Abnormalities - Week 48 and Cumulative Data	8; 8; 11; 10; 30; 22	—
SECONDARY Number of Participants With Alanine Aminotransferase (ALT) Flares - On Treatment	2; 1; 1; 0; 1; 1	—
SECONDARY Number of Participants With Malignant Neoplasms - On Treatment or During 24-Week Follow-up Period	14; 18; 12; 18; 1; 0	—
SECONDARY Number of Participants Undergoing Liver Transplant - On-Treatment or 24-Week Follow-Up	11; 3; 91; 86	—

Summary

This is a phase IIIb comparative study of entecavir 1.0 mg once daily (QD) vs. adefovir 10 mg QD in patients who have chronic hepatitis B infection and hepatic decompensation. The patients are treated for 96 weeks after the last subject is randomized.

Eligibility Criteria

Inclusion

Child-Pugh (CP) score >= 7
Hepatitis B virus (HBV) viremia

Exclusion

Alanine aminotransferase (ALT) > 15 x upper limit of normal (ULN)
Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)/hepatitis D virus (HDV) coinfection

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00065507). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.