Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone

An Open-label, Multicenter, Randomized Study of Combination Therapy With Oral LDT600 (Telbivudine) Plus Adefovir Dipivoxil Versus Adefovir Dipivoxil Alone in HBeAg-positive Patients With Chronic Hepatitis B Who Are Lamivudine Resistant

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: telbivudine; Drug: adefovir dipivoxil

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Pok Fu Lam, Hong Kong
• Korea, Republic of
  • Seoul, Korea, Republic of
• Taiwan
  • Kaohsuing, Taiwan
    • Novarits
• Thailand
  • Bangkok, Thailand
• United States
  • California
    • San Diego, California, United States
      • Novartis
    • San Mateo, California, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy; Combination therapy: 600 mg of telbivudine (LdT) by mouth plus 10 mg of adefovir (ADV) by mouth once daily for 96 weeks.	Drug: telbivudine; 600mg/day oral tablet for 96 weeks; Drug: adefovir dipivoxil; 10 mg of adefovir by mouth once daily
Active Comparator: Adefovir monotherapy; Adefovir monotherapy: 10 mg of adefovir by mouth once daily for 96 weeks.	Drug: adefovir dipivoxil; 10 mg of adefovir by mouth once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Participants Who Experienced Virologic Breakthrough	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.	96 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Hepatitis B Virus (HBV) DNA Concentration	Efficacy was assessed by the change from baseline in mean HBV DNA concentration after 12, 24, 48 and 60 weeks of treatment.	Baseline to 12 weeks, 24 weeks, 48 weeks and 60 weeks
Percentage of Participants Achieving Specified Clinical and Laboratory Safety Criteria	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.	12 week, 24 week, 48 week and 60 weeks
Proportion of Participants With Treatment-emergent HBV Resistance Mutations Associated With Virologic Breakthrough	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.	Week 96

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: September 13, 2006
• First Submitted That Met QC Criteria: September 13, 2006
• First Posted (Estimate): September 14, 2006

Study Record Updates

• Last Update Posted (Estimate): June 30, 2011
• Last Update Submitted That Met QC Criteria: June 28, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Hepatitis B virus; lamivudine resistance
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Telbivudine; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: CLDT600A2304