Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone

• ClinicalTrials.gov Identifier: NCT00376259
• Recruitment Status: Terminated
• First Posted: September 14, 2006
• Results First Posted: May 17, 2011
• Last Update Posted: June 30, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis B	Drug: telbivudine; Drug: adefovir dipivoxil	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2007
• Actual Primary Completion Date: August 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The Proportion of Participants Who Experienced Virologic Breakthrough [ Time Frame: 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 :

1. Change From Baseline in Mean Hepatitis B Virus (HBV) DNA Concentration [ Time Frame: 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.
2. Percentage of Participants Achieving Specified Clinical and Laboratory Safety Criteria [ Time Frame: 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.
3. Proportion of Participants With Treatment-emergent HBV Resistance Mutations Associated With Virologic Breakthrough [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Novartis

San Diego, California, United States

San Mateo, California, United States

Hong Kong

Pok Fu Lam, Hong Kong

Korea, Republic of

Seoul, Korea, Republic of

Taiwan

Novarits

Kaohsuing, Taiwan

Thailand

Bangkok, Thailand

Sponsors and Collaborators

Novartis

More Information

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00376259
• Other Study ID Numbers: CLDT600A2304
• First Posted: September 14, 2006
• Results First Posted: May 17, 2011
• Last Update Posted: June 30, 2011
• Last Verified: June 2011

Keywords provided by Novartis:

lamivudine resistance; Hepatitis B virus

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepadnaviridae Infections; DNA Virus Infections; Adefovir; Adefovir dipivoxil; Telbivudine; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents