Study of Combination Therapy With LdT Plus Adefovir Versus Adefovir Alone

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00376259
• Other study ID #: CLDT600A2304
• Status: Terminated
• Phase: Phase 3
• First received: September 13, 2006
• Last updated: June 28, 2011
• Start date: January 2007

Study information

• Verified date: June 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B

Intervention

Drug:
• telbivudine
600mg/day oral tablet for 96 weeks
• adefovir dipivoxil
10 mg of adefovir by mouth once daily

Locations

Country	Name	City	State
Taiwan	Novarits	Kaohsuing
United States	Novartis	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Hong Kong,  Korea, Republic of,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No