Continuing Lamivudine vs Switching to Entecavir in Patients With Detectable HBV DNA - Full Text View

Purpose

This is a randomized, open-labelled, prospective 96-week study comparing the antiviral efficacy and safety of switching to entecavir 1 mg QD from lamivudine versus maintaining lamivudine 100 mg QD treatment in HBV-infected subjects currently receiving lamivudine monotherapy.

Condition	Intervention	Phase
Hepatitis B, Chronic	Drug: Entecavir Drug: Lamivudine	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized, Open-Labelled Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Continuing Lamivudine Therapy or Switching to Entecavir in Subjects With Chronic Hepatitis B With Detectable HBV DNA

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Lamivudine Entecavir

U.S. FDA Resources

Further study details as provided by Yonsei University:

Primary Outcome Measures:

Percentage number of patients with HBV DNA < 60 IU/mL (Undetectable serum HBV DNA by PCR method) while on randomized therapy [ Time Frame: at Week 96 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percentage number of patients with HBV DNA < 60 IU/mL while on randomized therapy [ Time Frame: at Week 48 ] [ Designated as safety issue: No ]
Percentage number of patients who developed drug resistant mutations while on randomized therapy [ Time Frame: at Week 48 and Week 96 ] [ Designated as safety issue: No ]
Change from baseline in mean HBV DNA [ Time Frame: at Week 48 and 96 ] [ Designated as safety issue: No ]
Percentage number of patients who achieved ALT normalization, HBeAg loss, HBe seroconversion, HBsAg loss and HBs seroconversion [ Time Frame: at Week 48 and 96 ] [ Designated as safety issue: No ]
Cumulative discontinuation rates due to lamivudine or entecavir resistance mutations and clinical breakthrough Safety assessment [ Time Frame: Follow up period ] [ Designated as safety issue: Yes ]

Enrollment:	72
Study Start Date:	February 2008
Study Completion Date:	November 2010
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A entecavir 1.0 mg QD	Drug: Entecavir entecavir 1.0 mg QD Other Name: Baraclude 1.0mg
Active Comparator: B lamivudine 100 mg QD	Drug: Lamivudine lamivudine 100 mg QD Other Name: Zeffix 100mg

Detailed Description:

Entecavir has a higher potent antiviral efficacy and a lower drug resistance rate than Lamivudine in nucleoside-naïve CHB patients. The prompt switch from Lamivudine to Entecavir in patients who have insufficient hepatitis B virus suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to full viral suppression to undetectable level by PCR method. The prompt switch from Lamivudine to Entecavir in patients who have insufficient hepatitis B virus suppression (HBV DNA ≥ 60 IU/mL) may preclude development of drug resistance. The results of this study will provide a rationale for switch treatment from one antiviral to another one, especially from LAM to ETV.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult subjects (18-70 years of age) currently taking lamivudine monotherapy for chronic HBV infection for at least 6 months with ≥ HBV DNA 60 IU/mL level and HBeAg positive at baseline.

Exclusion Criteria:

All subjects will be tested for presence of M204V/I mutations in the YMDD motif at baseline. Subjects with M204V/I mutations in the YMDD motif at baseline are not eligible for the study.
Subjects treated with other antiviral drugs (e.g. adefovir) in combination with lamivudine are not eligible for this study.
Subjects should have ALT ＜ 10 x ULN, and no evidence of hepatocellular carcinoma.
Subjects should be without serological evidence of co-infection with HCV, HIV, or HDV.
Subjects with decompensated liver disease, as well as pregnant or breast-feeding women, will not be eligible for the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625560

Locations

Korea, Republic of
Pusan National University School of Medicine
Busan, Korea, Republic of, 602-739
Severance Hospital
Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

Yonsei University

Pusan National University Hospital

Investigators

Study Chair:	Sang Hoon Ahn, M.D.Ph.D	Yonsei Univsersity College of Medicine
Study Director:	Do Young Kim, M.D.	Yonsei University College of Medicine
Principal Investigator:	Jun Yong Park, M.D	Yonsei University College of Medicine
Study Director:	Jeong Heo, M.D.Ph.D	Pusan National University School of Medicine

More Information

No publications provided

Responsible Party:	Sang Hoon Ahn, Associate Professor, Yonsei University
ClinicalTrials.gov Identifier:	NCT00625560 History of Changes
Other Study ID Numbers:	4-2007-0351
Study First Received:	February 11, 2008
Last Updated:	May 7, 2012
Health Authority:	Korea: Food and Drug Administration

Keywords provided by Yonsei University:

Chronic hepatitis B
Lamivudine
Entecavir

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections

DNA Virus Infections
Lamivudine
Entecavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 16, 2013