Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs - Full Text View

Purpose

The purpose of this study is to evaluate the efficacy and safety of once-daily treatment with GSK548470 300 mg in Japanese patients with compensated chronic hepatitis B with poor response to other drugs.

Condition	Intervention	Phase
Hepatitis B, Chronic	Drug: GSK548470 300 mg tablet	Phase 3

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multi-center, Open-label Study of GSK548470 (Tenofovir Disoproxil Fumarate) in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Formic acid Tenofovir Tenofovir Disoproxil Fumarate Recombinant Hepatitis B vaccine Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Proportion of subjects with serum HBV DNA < 2.1 log10 copies/mL at week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean change of serum HBV DNA from baseline at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
Proportion of subjects with serum HBV DNA < 2.1 log10 copies/mL at week 48, 96 [ Time Frame: Week 48, 96 ] [ Designated as safety issue: No ]
Proportion of subjects with ALT normalization at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
Proportion of subjects achieving HBeAg loss, HBeAg /Ab seroconversion at week 24, 48, 96 in HBeAg positive subjects [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
Proportion of subjects achieving HBsAg loss and HBsAg/Ab seroconversion at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
Proportion of subjects with resistant mutation and/or virologic breakthrough (defined as HBV-DNA level increase >= 1 log10 copies/mL above the treatment nadir) at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
Reduction in quantitative HBsAg at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
Reduction in quantitative HBcrAg at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2014
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GSK548470 300 mg GSK548470 300 mg tablet is administered orally once daily	Drug: GSK548470 300 mg tablet Blue tablets containing 300 mg of tenofovir disoproxil fumarate Other Name: GSK548470

Detailed Description:

This is a multicenter, open-label study in Japanese patients with compensated chronic hepatitis B with poor response to other drugs in order to evaluate the efficacy and safety of GSK548470 administered at a dose of 300 mg once daily. The target sample size is set at 32 subjects. The primary objective is to evaluate the efficacy and safety of once-daily treatment with GSK548470 300 mg in subjects with compensated chronic hepatitis B with poor response to other drugs. The secondary objective is to evaluate the long-term efficacy and safety of once-daily treatment with GSK548470 300 mg.To evaluate the efficacy and safety of GSK548470 in the study, subjects receiving a combination of lamivudine (LAM) and adefovir pivoxil (ADV) will be switched to a combination of LAM and GSK548470, while subjects on entecavir hydrate (ETV) with or without ADV will be switched to a combination of ETV and GSK548470.

Eligibility

Ages Eligible for Study:	16 Years to 69 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The ability to understand and sign a written informed consent form
16 to 69 years of age at the time of informed consent
Females of childbearing potential must have a negative pregnancy test and agree to avoidance of pregnancy
Subject must show QTc <450 millisecond (msec) or <480msec with Bundle Branch Block
Chronic HBV infection, defined as positive serum HBsAg for at least 6 month
Subjects currently treated with LAM/ADV, ETV or ETV/ADV for greater than 24 weeks
Chronic hepatitis B ; HBV NDA >= 4 log10 copies/mL, Chronic hepatitis B with cirrhosis ; HBV NDA >= 3 log10 copies/mL
Serum ALT <= 10 × ULN
Creatinine clearance >= 70 mL/min
Haemoglobin >= 8 g/dL
WBC >= 1,000 /mm3

Exclusion Criteria:

Decompensated liver disease
Co-infection with HIV or HCV
Autoimmune hepatitis rather than chronic hepatitis B
Subject with serious complication
Received or have a plan for solid organ or bone marrow transplantation
Has proximal tubulopathy
History of hypersensitivity to nucleoside and/or nucleotide analogues
Evidence of hepatocellular carcinoma by diagnostic imaging at screening and/or serum α-fetoprotein > 50 ng/mL at screening
History of HCC
Received any interferon or HB vaccine therapy within 24 weeks prior to initiation
Received overdose NSAIDs, excluding temporary or topical use, within 7 days prior to initiation
Received drugs for injection containing glycyrrhizin as the main component within 4 weeks prior to initiation
Received drugs causing renal impairment, competitors of renal excretion, immunosuppressants, chemotherapeutics and/or corticosteroids within 8 weeks prior to initiation
Participation in another clinical study within 6 months of study entry or planned participation in another clinical study after entry to this study
Woman who is pregnant, lactating, possibly pregnant or planning a pregnancy during the study period
Psychiatry disorder or cognitive disorder that may affect the subject ability to give informed consent or to follow specified study procedures
History of alcohol or drug abuse
Any condition or situation that may interfere with the subject's participation in the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475851

Locations

Japan
GSK Investigational Site
Aichi, Japan, 466-8560
GSK Investigational Site
Aichi, Japan, 467-8602
GSK Investigational Site
Chiba, Japan, 260-8677
GSK Investigational Site
Fukuoka, Japan, 803-8505
GSK Investigational Site
Hiroshima, Japan, 734-8551
GSK Investigational Site
Hokkaido, Japan, 060-0033
GSK Investigational Site
Kagoshima, Japan, 890-8520
GSK Investigational Site
Kanagawa, Japan, 213-8587
GSK Investigational Site
Miyagi, Japan, 980-8574
GSK Investigational Site
Tokyo, Japan, 105-8470
GSK Investigational Site
Tokyo, Japan, 180-8610

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01475851 History of Changes
Other Study ID Numbers:	115912
Study First Received:	November 17, 2011
Last Updated:	May 16, 2013
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by GlaxoSmithKline:

Tenofovir disoproxil fumarate, compensated chronic hepatitis B

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
Tenofovir
Tenofovir disoproxil
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 19, 2013