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Safety and Efficacy Study of LB80380 in the Patients With Lamivudine-Refractory Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by:
LG Life Sciences
ClinicalTrials.gov Identifier:
NCT00895596
First received: May 7, 2009
Last updated: NA
Last verified: May 2009
History: No changes posted
  Purpose

The purpose of the study is to investigate the safety and the antiviral activity of ascending multiple oral doses of LB80380 for 12 weeks in adults with lamivudine-refractory chronic hepatitis B infection.


Condition Intervention Phase
Chronic Hepatitis B
 Drug: LB80380
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PhaseII, Open-Label, Multinational, Multi-Centre, Sequential Group, Dose-Escalation Study to Assess the Safety and Antiviral Activity of LB80380 for 12 Weeks in Patients With Lamivudine-Refractory Chronic Hepatitis B

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by LG Life Sciences:

Primary Outcome Measures:
  • Mean serum HBV DNA level (log10) reduction from the baseline at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with HBeAg seroconversion at 12 weeks Proportion of patients with HBsAg seroconversion at 12 weeks Proportion of patients with ALT normalization at 12 weeks Safety assessment during the whole study period [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]

Enrollment: 65
Study Start Date: March 2004
Study Completion Date: December 2007
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LB80380 30mg
LB80380 30mg
 Drug: LB80380
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
Other Name: Not available
Experimental: LB80380 60mg
LB80380 60mg
 Drug: LB80380
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
Other Name: Not available
Experimental: LB80380 90mg,
LB80380 90mg
 Drug: LB80380
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
Other Name: Not available
Experimental: LB80380 150mg
LB80380 150mg
 Drug: LB80380
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
Other Name: Not available
Experimental: LB80380 240mg
LB80380 240mg
 Drug: LB80380
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
Other Name: Not available

Detailed Description:

LB80380, an oral prodrug, is a promising candidate nucleoside analogue with antiviral activity against wild-type HBV. LB80380 is undergoing clinical development by LG Life Sciences for use in the treatment of chronic HBV infection and for treatment of lamivudine-resistant disease.

In this study, the treatment period was divided into two parts: a 4-week treatment period with dose escalation assessment (Part 1), followed by an 8-week extension period (Part 2).

During Part 1, patients received LB80380 and LVD 100 mg once daily for 4 weeks. Each patient was then given only LB80380 for an additional 8 weeks (Part 2) unless dose-limiting toxicity (DLT) was observed during Part 1. At each dose level, all patients were to complete at least Part 1 of the treatment period before enrolment into the next Dose Group could commence. Dose escalation to the next group was not to be initiated if more than two patients experienced DLT during Part 1 in the previous Dose Group. Additionally, patients enrolled in LB80380 150mg and 240mg groups who agreed to participate in the pharmacokinetic (PK) analyses visited the study site the day before Week 12 for blood sampling. Follow-up period was 24 weeks, and patients were treated with adefovir dipivoxil during the follow-up period. During the study, patients were evaluated for changes from baseline in serum HBV DNA. Safety was evaluated on the basis of occurrence of AEs and changes from baseline in clinical laboratory parameters, physical examination findings, and vital signs.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Compensated chronic hepatitis B patient
  • Presence of serum HBsAg for more than 6 months.
  • Presence of HBeAg for more than 1 month with compensated liver disease
  • Confirmation of YMDD mutants (M552V, M552I and its related double mutant at L528M) by genotyping of the YMDD motif using line probe assay (INNO-LiPA HBV DR assay)
  • Screening HBV DNA value higher than or equal to 1,000,000 copies/mL (measured by the COBAS Amplicor HBV Monitor™ assay)
  • Screening ALT value between 1.5 and 10 x ULN

Exclusion Criteria:

  • Co-infection with hepatitis C or D virus (HCV or HDV) or HIV
  • Pregnancy or breast-feeding
  • Previous treatment with nucleoside analogue or any other treatment for HBV except for lamivudine within 6 months prior to study entry
  • Treatment with immunomodulatory agent or corticosteroids within 6 months prior to study entry.
  • De-compensated liver disease
  • Screening alpha-fetoprotein (AFP) value > 20 ng/mL, and a follow-up ultrasonography performed prior to baseline shows findings indicative of HCC.
  • Presence of anti-HBs at screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00895596

Locations
China
Queen Mary Hospital
Hong Kong, China
Korea, Republic of
Severance Hospital of Yonsei University
Seoul, Korea, Republic of
The Catholic University of Korea, Kangnam St. Mary's Hospital
Seoul, Korea, Republic of
Korea University Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
LG Life Sciences
Investigators
Principal Investigator: Ching-Lung Lai, Dr Queen Mary Hospital, Hong Kong
  More Information

No publications provided by LG Life Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: LG Life Sciences, Ltd.
ClinicalTrials.gov Identifier: NCT00895596     History of Changes
Other Study ID Numbers: BVCL004
Study First Received: May 7, 2009
Last Updated: May 7, 2009
Health Authority: United States: Food and Drug Administration
Korea: Food and Drug Administration

Keywords provided by LG Life Sciences:
Chronic hepatitis B
Lamivudine resistant
YMDD mutant type

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
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 June 13, 2013