Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone

This study has been terminated.
(The study was not completed as planned and was terminated early with agreement from the European Medicines Agency (EMEA))
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00376259
First received: September 13, 2006
Last updated: June 28, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Hepatitis B
Drug: telbivudine
Drug: adefovir dipivoxil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Proportion of Participants Who Experienced Virologic Breakthrough [ Time Frame: 96 Weeks ] [ Designated as safety issue: Yes ]
    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:
  • Change From Baseline in Mean Hepatitis B Virus (HBV) DNA Concentration [ Time Frame: Baseline to 12 weeks, 24 weeks, 48 weeks and 60 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 12 week, 24 week, 48 week and 60 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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.


Enrollment: 43
Study Start Date: January 2007
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: adefovir dipivoxil
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
Other Name: adefovir dipivoxil

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376259

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

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00376259     History of Changes
Other Study ID Numbers: CLDT600A2304
Study First Received: September 13, 2006
Results First Received: December 20, 2010
Last Updated: June 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
lamivudine resistance
Hepatitis B virus

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
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
Lamivudine
Telbivudine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 19, 2014