Overview

This trial is active, not recruiting.

Condition hepatitis b, chronic
Treatments gsk548470 300 mg tablet, etv 0.5 mg capsule
Phase phase 3
Sponsor GlaxoSmithKline
Start date November 2011
End date January 2013
Trial size 166 participants
Trial identifier NCT01480284, 115409

Summary

The purpose of this study is to evaluate the efficacy and safety of GSK548470 administered once daily at a dose level of 300 mg to Japanese patients with compensated chronic hepatitis B untreated with any nucleic acid analogue. In efficacy, the non-inferiority of GSK548470 to ETV will be verified using the antiviral effect as the index.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
GSK548470 300 mg tablet and ETV placebo capsule are administered once daily
gsk548470 300 mg tablet GSK548470
Blue tablets, each tablet containing 300 mg of tenofovir disoproxil fumarate
(Active Comparator)
ETV 0.5 mg capsule and GSK548470 placebo tablet are administered once daily
etv 0.5 mg capsule ETV
Brown capsules, each capsule containing 0.53 mg of entecavir hydrate

Primary Outcomes

Measure
Mean Change From Baseline in Serum HBV DNA Level at Week 24
time frame: Baseline and Week 24

Secondary Outcomes

Measure
Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96
time frame: Baseline, Week 48 and Week 96
Number of Participants With Serum HBV DNA <2.1 log10 Copies/mL at Week 24
time frame: Week 24
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24
time frame: Week 24
Number of Participants With HBeAg Loss at Week 24
time frame: Week 24
Number of Participants With HBeAg/HBeAb Seroconversion at Week 24
time frame: Week 24
Number of Participants Achieving HBsAg Loss at Week 24
time frame: Week 24
Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24
time frame: Week 24
Number of Participants Achieving Each Indicated HBsAg Category at Baseline and Week 24
time frame: Baseline and Week 24
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline and Week 24
time frame: Baseline and Week 24
Number of Participants With Virological Breakthrough Through Weeks 24
time frame: Week 24
Number of Participants With Resistance Related Mutations at Week 24
time frame: Week 24

Eligibility Criteria

Male or female participants from 16 years up to 69 years old.

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 < 480 msec with Bundle Branch Block - Chronic HBV infection, defined as positive serum HBsAg for at least 6 month, or negative serum IgM-HBc antibody - HBeAg positive; HBV-DNA >= 6 log10 copies/mL, HBeAg negative; HBV-DNA >= 5 log10 copies/mL - Serum ALT >= 31 U/L and <= 10 × ULN - Creatinine clearance >= 70 mL/min - Haemoglobin >= 8 g/dL - WBC >= 1,000 /mm3 - Nucleic acid analogue naïve, i.e., no prior therapy for over 6 months in the past - No mutation that shows resistance in LAM, ETV and/or TDF at screening 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 nucleoside, nucleotide, 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

Additional Information

Official title A Multi-center, Randomized, Active Controlled, Double-blind, Parallel Group Comparison Study and Subsequent Open-label Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue
Description This study is a multicenter, randomized, active comparator-controlled, double-blind, parallel-group comparison study in Japanese patients with compensated chronic hepatitis B untreated with any nucleic acid analogue and its subsequent open-label study. Efficacy and safety will be compared between once-daily dosing of GSK548470 300 mg and once-daily dosing of ETV 0.5 mg, and subsequently the efficacy and safety of GSK548470 administered long term will be investigated. A total of 165 subjects will be assigned to the GSK548470 group or the ETV group at a ratio of 2:1. The subjects will be assigned by stratified randomization in terms of HBe antigen and serum HBV-DNA level. The primary purpose is to verify the non-inferiority of GSK548470 to ETV using as an index the change amount of HBV-DNA level at Week 24 from the baseline level. The secondary purpose is to investigate the efficacy and safety of GSK548470 300 mg administered once daily for a long term.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.