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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01475851
First received: November 17, 2011
Last updated: June 18, 2015
Last verified: May 2015
  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:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Change From Baseline in Serum HBV DNA Level at Week 24, Week 48 and Week 96 [ Time Frame: Baseline and Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 48 and Week 96 [ Time Frame: Week 48 and Week 96 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants achieving hepatitis Be antigen (HBeAg) loss at Week 24, Week 48 and Week 96 in positive HBeAg participants at Baseline were summarized. Loss of HBeAg is defined as the change of detectable HBeAg from positive to negative. The LOCF method was applied for missing values.

  • Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants achieving hepatitis Be antigen (HBeAg)/hepatitis B e antibody (HBeAb) seroconversion at Week 24, Week 48 and Week 96 in positive HBeAg and negative HBeAb participants at Baseline were summarized. Seroconversion to HBeAg is defined as change of detectable antibody to HBeAg from negative to positive. The LOCF method was applied for missing values.

  • Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants with hepatitis B surface antigen (HBsAg) loss at Week 24, Week 48 and Week 96 in positive HBsAg participants at Baseline were summarized. Loss of HBsAg is defined as change of detectable HBsAg from positive to negative. The LOCF method was applied for missing values.

  • Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants with hepatitis B surface antigen (HBsAg)/hepatitis B surface antibody (HBsAb) seroconversion at Week 24, Week 48 and Week 96 in positive HBsAg and negative HBsAb participants at Baseline were summarized. HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. The LOCF method was applied for missing values.

  • Number of Participants With Virological Breakthrough and Resistance-related Mutations [ Time Frame: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough ] [ Designated as safety issue: No ]
    The number of participants who harbored resistance-related mutations and developed virological breakthrough was summarized. Virological breakthrough defined as HBV DNA level increase >=1 log10 copies/mL above the treatment nadir were analyzed through end of treatment. Subjects who achieved the HBV-DNA values below lower limit of quantification (LLQ) (< 2.1 log10 copies/mL) in quantitative analysis at Week 96 were also considered "negative" in drug-resistance without implementation of genotypic analysis. Lamivudine (LAM), adefovir pivoxil (ADV), and entecavir hydrate (ETV) resistance-related mutations were analyzed at Screening (i.e. Baseline), Week 24, Week 48 and Week 96 in participants with HBV DNA level above the lower limit of detection. Virologic breakthrough was defined as 1.0 log10 or greater increases in serum HBV DNA levels from on-treatment nadir. The LOCF method was applied for missing values.

  • Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 [ Time Frame: Baseline, Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants achieving each indicated hepatitis B surface antigen (HBsAg) category (HBsAg <80, 80 to 800, 800 to 8000, 8000 to 80000, >=80000) (kilo international unit per liter [KIU/L]) by study visit was summarized.

  • Number of Participants Achieving Each Indicated HBcrAg Category at Baseline,Week 24, Week 48 and Week 96 [ Time Frame: Baseline, Week 24, Week 48 and Week 96 ] [ Designated as safety issue: No ]
    The number of participants achieving each indicated hepatitis B core-related antigen (HBcrAg) category (HBcrAg <3.0 log10, 3.0 to 4.0 log10, 4.0 to 5.0 log10, 5.0 to 6.0 log10, >=6.0 log10) (kilo units per liter [KU/L]) by study visit was summarized. The LOCF method was applied for missing values.


Enrollment: 34
Study Start Date: December 2011
Study Completion Date: October 2014
Primary Completion Date: June 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Results First Received: August 22, 2013
Last Updated: June 18, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by GlaxoSmithKline:
Tenofovir disoproxil fumarate, compensated chronic hepatitis B

Additional relevant MeSH terms:
Hepatitis B, Chronic
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015