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

NCT ID: NCT01475851

Last Updated: 2015-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2014-10-31

Brief Summary

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.

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.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GSK548470 300 mg

GSK548470 300 mg tablet is administered orally once daily

Group Type: EXPERIMENTAL

GSK548470 300 mg tablet

Intervention Type: DRUG

Blue tablets containing 300 mg of tenofovir disoproxil fumarate

Interventions

GSK548470 300 mg tablet

Blue tablets containing 300 mg of tenofovir disoproxil fumarate

Intervention Type: DRUG

Other Intervention Names

GSK548470

Eligibility 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hiroshima, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Kagoshima, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

Countries

Japan

References

Kumada H, Koike K, Suyama K, Ito H, Itoh H, Sugiura W. Efficacy and safety of tenofovir disoproxil fumarate rescue therapy for chronic hepatitis B patients who failed other nucleos(t)ide analogs. Hepatol Res. 2017 Sep;47(10):1032-1041. doi: 10.1111/hepr.12842. Epub 2016 Dec 21.

Reference Type: DERIVED

PMID: 27862721 (View on PubMed)

Other Identifiers

115912

Identifier Type: -

Identifier Source: org_study_id