Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone

Phase 3

Terminated

Conditions: Hepatitis B

Interventions: Drug: telbivudine
Drug: adefovir dipivoxil

Registration Number: NCT00376259

Lead Sponsor: Novartis

Brief Summary: This study is being conducted to compare the safety and effectiveness of the investigational medication LdT (telbivudine) used in combination with adefovir dipivoxil (a drug currently approved by the Food and Drug Administration \[FDA\] for the treatment of hepatitis B virus \[HBV\]) versus adefovir dipivoxil used alone. The results for patients taking the combination therapy will be compared to the results for patients taking adefovir alone.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 43

Inclusion Criteria

Documented compensated chronic hepatitis B defined by a clinical history compatible with chronic hepatitis B.
Previous or current lamivudine treatment
HBV DNA > 6 log10 copies/mL
Evidence of viral breakthrough

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria

Patient is pregnant or breastfeeding.
Patient is co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV.
Patient has received any anti-HBV treatment for HBV infection other than lamivudine in the 12 months before Screening for this study.

Other protocol-defined exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination therapy	adefovir dipivoxil	Combination therapy: 600 mg of telbivudine (LdT) by mouth plus 10 mg of adefovir (ADV) by mouth once daily for 96 weeks.
Combination therapy	telbivudine	Combination therapy: 600 mg of telbivudine (LdT) by mouth plus 10 mg of adefovir (ADV) by mouth once daily for 96 weeks.
Adefovir monotherapy	adefovir dipivoxil	Adefovir monotherapy: 10 mg of adefovir by mouth once daily for 96 weeks.

Primary Outcome Measures

Name	Time	Method
The Proportion of Participants Who Experienced Virologic Breakthrough	96 Weeks	Virologic breakthrough is defined as a minimum of 1 log reduction from baseline followed by a 1 log increase from nadir on at least 2 consecutive visits including the last treatment visit.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Hepatitis B Virus (HBV) DNA Concentration	Baseline to 12 weeks, 24 weeks, 48 weeks and 60 weeks	Efficacy was assessed by the change from baseline in mean HBV DNA concentration after 12, 24, 48 and 60 weeks of treatment.
Percentage of Participants Achieving Specified Clinical and Laboratory Safety Criteria	12 week, 24 week, 48 week and 60 weeks	Undetectable HBV DNA = HBV DNA \<300 copies/ml. Serum aminotransferase (ALT) normalization is defined as ALT within normal limits on 2 successive visits for a pt. with an elevated ALT level (\>=1.0 x ULN) at baseline (BL). Hepatitis B e antigen (HBeAg) loss is defined as the loss of detectable serum HBeAg in a pt. who was HBeAg +ve at BL. HBeAg seroconversion is defined as HBeAg loss with detectable HBeAb. Hepatitis B surface antigen (HBsAg) loss is defined as the loss of detectable serum HBsAg in a pt. who was HBsAg +ve at BL. HBsAg seroconversion is defined as HBsAg loss with detectable HBsAb.
Proportion of Participants With Treatment-emergent HBV Resistance Mutations Associated With Virologic Breakthrough	Week 96	The study was not completed as planned and was terminated early with agreement from the European Medicines Agency (EMEA). Patients did not receive 96 weeks of treatment. Therefore, the primary objective of evaluating virologic breakthrough by Week 96 could not be assessed. Consequently, all protocol-specified inferential analyses on the primary endpoint and all other key secondary efficacy endpoints could not be performed.