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

GlaxoSmithKline34 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis B, Chronic

Interventions

GSK548470 300 mg tabletDRUG

Blue tablets containing 300 mg of tenofovir disoproxil fumarate

Eligibility

Sex: ALLMin age: 16 YearsMax age: 69 Years

Medical Language ↔ Plain English

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

Locations (11)

GSK Investigational Site

Aichi, Japan

GSK Investigational Site

Aichi, Japan

GSK Investigational Site

Chiba, Japan

GSK Investigational Site

Fukuoka, Japan

Outcomes

Primary Outcomes

Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24

The number of participants with serum hepatitis B virus deoxyribonucleic acid (HBV DNA) level \< the lower limit of quantitation (2.1 log10 copies/millilitres\[copies/mL\]) (i.e., the rate of suppression) at Week 24 was summarized. Statistical analysis was not provided for the number of participants achieving HBV DNA \<2.1 log10 copies/mL (at Week 24). Missing values observed during the treatment period was imputed by the last observation carried forward (LOCF) method.

Time frame: Week 24

Secondary Outcomes

Mean Change From Baseline in Serum HBV DNA Level at Week 24, Week 48 and Week 96

The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24, Week 48 and Week 96 were assessed (HBV DNA values below the lower limit of quantitation \[i.e. 2.1 log10 copies/mL\] for the assay were set to the lower limit minus 0.1 \[i.e. 2.0 log10 copies/mL\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Last Observation Carried Forward (LOCF) method was applied for missing values.

Time frame: Baseline and Week 24, Week 48 and Week 96

Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 48 and Week 96

The number of participants with serum HBV DNA level \< the lower limit of quantitation (2.1 log10 copies/mL) (i.e., the rate of suppression) at Week 48 and Week 96 were summarized. The LOCF method was applied for missing values.

Time frame: Week 48 and Week 96

Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96

The number of participants with alanine aminotransferase (ALT) normalization at Week 24, Week 48 and Week 96 were summarized. ALT normalization is defined as when an ALT value exceeds the upper limit of normal range (ULN) at Baseline and within the normal range at the end of treatment. The LOCF method was applied for missing values.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.