Back to resultsStudy of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone
Primary Purpose
Hepatitis B
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
telbivudine
adefovir dipivoxil
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B focused on measuring lamivudine resistance, Hepatitis B virus
Eligibility 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.
Sites / Locations
- Novartis
- Novarits
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Combination therapy
Adefovir monotherapy
Arm Description
Combination therapy: 600 mg of telbivudine (LdT) by mouth plus 10 mg of adefovir (ADV) by mouth once daily for 96 weeks.
Adefovir monotherapy: 10 mg of adefovir by mouth once daily for 96 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00376259
Brief Title
Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone
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 Type
Interventional
2. Study Status
Record Verification Date
June 2011
Overall Recruitment Status
Terminated
Why Stopped
The study was not completed as planned and was terminated early with agreement from the European Medicines Agency (EMEA)
Study Start Date
January 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B
Keywords
lamivudine resistance, Hepatitis B virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combination therapy
Arm Type
Experimental
Arm Description
Combination therapy: 600 mg of telbivudine (LdT) by mouth plus 10 mg of adefovir (ADV) by mouth once daily for 96 weeks.
Arm Title
Adefovir monotherapy
Arm Type
Active Comparator
Arm Description
Adefovir monotherapy: 10 mg of adefovir by mouth once daily for 96 weeks.
Intervention Type
Drug
Intervention Name(s)
telbivudine
Intervention Description
600mg/day oral tablet for 96 weeks
Intervention Type
Drug
Intervention Name(s)
adefovir dipivoxil
Intervention Description
10 mg of adefovir by mouth once daily
Primary Outcome Measure Information:
Title
The Proportion of Participants Who Experienced Virologic Breakthrough
Description
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.
Time Frame
96 Weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Hepatitis B Virus (HBV) DNA Concentration
Description
Efficacy was assessed by the change from baseline in mean HBV DNA concentration after 12, 24, 48 and 60 weeks of treatment.
Time Frame
Baseline to 12 weeks, 24 weeks, 48 weeks and 60 weeks
Title
Percentage of Participants Achieving Specified Clinical and Laboratory Safety Criteria
Description
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.
Time Frame
12 week, 24 week, 48 week and 60 weeks
Title
Proportion of Participants With Treatment-emergent HBV Resistance Mutations Associated With Virologic Breakthrough
Description
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.
Time Frame
Week 96
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Novartis
City
San Diego
State/Province
California
Country
United States
City
San Mateo
State/Province
California
Country
United States
City
Pok Fu Lam
Country
Hong Kong
City
Seoul
Country
Korea, Republic of
Facility Name
Novarits
City
Kaohsuing
Country
Taiwan
City
Bangkok
Country
Thailand
12. IPD Sharing Statement
Learn more about this trial
Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone
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