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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00244751




Registration number
NCT00244751
Ethics application status
Date submitted
25/10/2005
Date registered
27/10/2005
Date last updated
11/12/2017

Titles & IDs
Public title
Antifibrotic Activity Of GI262570 In Chronic Hepatitis C Subjects
Scientific title
A Double-Blind, Randomized, Placebo-Controlled Multi-Center, Phase II Parallel Dose-Ranging Study to Assess the Antifibrotic Activity of GI262570 in Chronic Hepatitis C Subjects With Hepatic Fibrosis Who Have Failed Prior Antiviral Therapy
Secondary ID [1] 0 0
FBX104114
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cirrhosis, Liver 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GI262570 0.5 mg
Treatment: Drugs - GI262570 1.0 mg
Treatment: Drugs - Placebo

Experimental: GI262570 0.5 mg - Participants received GI262570 0.5 milligrams (mg) tablet once daily approximately 30 minutes prior to breakfast for 52 weeks. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.

Experimental: GI262570 1.0 mg - Participants received GI262570 1.0 mg tablet once daily approximately 30 minutes prior to breakfast for 52 weeks. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.

Placebo Comparator: Placebo - Participants received matching placebo tablet once daily approximately 30 minutes prior to breakfast for 52 weeks. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.


Treatment: Drugs: GI262570 0.5 mg
GI262570 0.5 mg

Treatment: Drugs: GI262570 1.0 mg
GI262570 1.0 mg

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Liver Biopsy Immunohistochemical Marker of Hepatic Stellate Cell (HSC) Activation and Collagen Synthesis at Week 52
Timepoint [1] 0 0
Baseline and Week 52
Primary outcome [2] 0 0
Mean Change From Baseline in Fibrosis as Quantified by Morphometric Image Analysis
Timepoint [2] 0 0
Baseline and at Week 52
Primary outcome [3] 0 0
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52
Timepoint [3] 0 0
Week 52
Primary outcome [4] 0 0
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [4] 0 0
Up to 4 weeks post treatment (52 weeks)
Primary outcome [5] 0 0
Number of Participants With Abnormal ECG Findings
Timepoint [5] 0 0
Up to 4 weeks post-treatment (52 weeks)
Primary outcome [6] 0 0
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time
Timepoint [6] 0 0
Up to 4 weeks post-treatment (52 weeks)
Primary outcome [7] 0 0
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSP)
Timepoint [7] 0 0
Baseline and up to 4 weeks post-treatment (52 weeks)
Primary outcome [8] 0 0
Mean Change From Baseline in Heart Rate
Timepoint [8] 0 0
Baseline and up to 4 weeks post-treatment (52 weeks)
Primary outcome [9] 0 0
Number of Participants With Fluid Retention Events
Timepoint [9] 0 0
Up to 4 weeks post-treatment (52 weeks)
Secondary outcome [1] 0 0
Number of Participants Progressing at Least 1 Point on the Ishak Fibrosis Score at Week 52
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
Number of Participants Regressing at Least 1 Point on the Ishak Fibrosis Score at Week 52
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Number of Participants Whose Ishak Fibrosis Score Remains Unchanged at Week 52
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Mean Change From Screening in Total Ishak Score (Necroinflammatory Score and Fibrosis Score) at Week 52
Timepoint [4] 0 0
Screening and Week 52
Secondary outcome [5] 0 0
Mean Change From Screening in Metavir Scores at Week 52
Timepoint [5] 0 0
Screening and Week 52
Secondary outcome [6] 0 0
Mean Change From Baseline in Serum FibroSure (FibroTest/ActiTest) Score at Week 52
Timepoint [6] 0 0
Baseline and Week 52
Secondary outcome [7] 0 0
Mean Change From Baseline in Serum ALT Levels
Timepoint [7] 0 0
Baseline and Week 52
Secondary outcome [8] 0 0
Mean Change From Baseline in Measures of Insulin Resistance
Timepoint [8] 0 0
Baseline and Week 52
Secondary outcome [9] 0 0
Median Change From Baseline in Serum ALT Over Time
Timepoint [9] 0 0
Baseline and up to 4 weeks post-treatment (52 weeks)
Secondary outcome [10] 0 0
Mean Change From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 52
Timepoint [10] 0 0
Baseline and Week 52
Secondary outcome [11] 0 0
Median Change From Baseline in Serum HCV RNA Levels Over Time
Timepoint [11] 0 0
Baseline and up to 4 weeks post-treatment (52 weeks)
Secondary outcome [12] 0 0
Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length 'Tau' (AUC [0-tau]) of GI262570 on Week 2
Timepoint [12] 0 0
At 0 (pre-morning dose)1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [13] 0 0
Dose Normalized (DN) AUC (0-tau) of GI262570 on Week 2
Timepoint [13] 0 0
At 0 (pre-morning dose )1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [14] 0 0
Apparent Clearance Following Oral Dosing (CL/F) of GI262570 on Week 2
Timepoint [14] 0 0
At 0 (pre-morning dose)1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [15] 0 0
Maximum Observed Concentration (Cmax), Minimum Observed Concentration (Cmin) of GI262570 on Week 2
Timepoint [15] 0 0
At 0 (pre-morning dose)1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [16] 0 0
DN Cmax of GI262570 on Week 2
Timepoint [16] 0 0
At 0 (pre-morning dose) 1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [17] 0 0
Terminal Elimination Half-life (T1/2), Time to First Quantifiable Concentration (Tlag) and Time to Cmax (Tmax) of GI262570 on Week 2
Timepoint [17] 0 0
At 0 (pre-morning dose)1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [18] 0 0
Volume of Distribution Expressed as a Function of Bioavailability (V/F) of GI262570
Timepoint [18] 0 0
At 0 (pre-morning dose)1, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hour post-morning dose on Week 2
Secondary outcome [19] 0 0
GI262570 Serum Concentrations on Week 2, 16, 28, 40, and Week 52
Timepoint [19] 0 0
Weeks 2, 16, 28, 40 and 52

Eligibility
Key inclusion criteria
Inclusion criteria:

- A subject will be eligible for inclusion in this study only if all of the following
criteria apply:

- Age between 40 and 70 years, inclusive.

- Documented positive serology for HCV antibody by a second generation or higher assay.

- Serum HCV RNA positive and HCV viral Genotype 1 at pre-screening visit.

- Ishak fibrosis score of 2, 3 or 4.

- Failure to achieve sustained virologic response (SVR) with previous interferon
(standard or pegylated) and ribavirin treatment administered at a minimum dose of 3mU
three times weekly or equivalent, for at least 12 weeks. Reasons for failure may
include failure to respond to treatment or intolerability to optimal treatment. Prior
treatment with interferon/ribavirin must have been discontinued at least 11 months
prior to the biopsy date.

- Male or female; a female is eligible to enter and participate in this study if she is
of:

1. non-childbearing potential (i.e., physiologically incapable of becoming pregnant,
including any female who is post-menopausal); or,

2. child-bearing potential, has a negative serum pregnancy test at screen, and
agrees to one of the following:

- Complete abstinence from intercourse from 2 weeks prior to administration of
the study drug, throughout the study, and for a time interval after
completion or premature discontinuation from the study to account for
elimination of the investigational drug, (a minimum of 5 half-lives or
longer if the pharmacodynamic profile of the investigational drug warrants a
longer time period); or,

- Female sterilization; or,

- Has a male partner who is sterilized; or,

- Implants of levonorgestrel; or,

- Injectable progestogen; or,

- Oral contraceptive (combined or progestogen only) , must be stable for 3
months prior to study entry; or,

- Any intrauterine device (IUD) with published data showing that the lowest
expected failure rate is less than 1% per year (not all IUDs meet this
criterion); or,

- Any other methods with published data showing that the lowest expected
failure rate for that method is less than 1% per year; or,

- Barrier method only if used in combination with any of the above acceptable
methods.

- Availability and willingness of subject to provide written informed consent.
Minimum age
40 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria
apply:

- History of ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial
peritonitis or other signs of hepatic decompensation.

- Current or historical evidence suggestive of ischemic heart disease or other
cardiovascular disease that in the investigator's opinion may adversely impact the
safety of the subject during the conduct of the study. Evidence suggestive of
cardiovascular disease may come from a number of sources, including clinical history,
physical exam, electrocardiogram, laboratory testing, and radiographic procedures.

- New York Heart Association (NYHA) Functional Class 1, 2, 3, or 4 cardiac status

- Co-infection with HBV or HIV.

- Liver histology consistent with any other co-existing cause of chronic liver disease.

- Documented evidence of a hepatic mass lesion suspicious for hepatocellular carcinoma.

- Alpha-fetoprotein > 200ng/mL at pre-screening.

- Inadequate hematologic function defined by any of the following:

Hemoglobin (<12.5 g/dL for men)(<12.0 g/dL for women)

Absolute Neutrophil Count (ANC) (<1.0 x 10^9/L) Platelets (<130X/10^9/L)

- Inadequate renal function defined as:

Serum creatinine (>1.5mg/dL (=130mmol/L)) Calculated creatinine clearance as calculated by
Cockcroft and Gault (<60mL/min)

- Serum ALT level =5 x ULN.

- Albumin <3.2g/dL.

- Total bilirubin >1.2 x ULN.

- Prothrombin time > 15 seconds or International normalized ratio (INR) > 1.3.

- Organ, stem cell, or bone marrow transplant.

- Serious concurrent medical illness that in the investigator's opinion might interfere
with therapy. This includes significant systemic illnesses (other than liver disease)
such as chronic pancreatitis.

- Active systemic autoimmune disorder.

- A pre-existing condition interfering with normal gastrointestinal anatomy or motility,
and/or renal function that could interfere with the absorption, metabolism, and/or
excretion of the study drugs.

- Other medical conditions that, in the investigator's opinion, might interfere with
compliance with therapy, participation in the study or interpretation of results.

- Pregnancy (or lactation) or, in subjects capable of bearing children,
inability/unwillingness to practice adequate contraception.

- Females of child-bearing potential (post-puberty) unwilling or unable to have
pregnancy testing at any study visit.

- Therapy with systemic cytotoxic agents, immunomodulators, or immunosuppressive therapy
requiring use of more than 5mg of prednisone (or its equivalent) per day.

- Therapy with a systemic antiviral agent (with the exception of prophylaxis or
treatment of influenza or chronic HSV) within the past 30 days.

- Concurrent participation in another clinical trial in which the subject is or will be
exposed to another investigational or a non-investigational drug or device within 30
days of the screening visit.

- Current therapy or anticipated need for therapy with hypoglycemic drugs (e.g.,
insulin, sulfonylurea or metformin).

- Known hypersensitivity to GI262570, or to any component of the GI262570 soft gelatin
capsules, dispersion tablets or the sodium salt tablet or to PPARg agonists.

- A history of hepatotoxicity to TZDs and/or a history of severe edema or medically
serious fluid-related events associated with the use of TZDs.

- Use of other PPAR agonists (e.g., rosiglitazone, pioglitazone) within 1 year from the
start of dosing.

- Active alcohol abuse within the past 1 year.

- Use of illegal drugs in the past 1 year. 30a. Macular edema or history of macular
edema.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/11/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/03/2008
Sample size
Target
Accrual to date
Final
265
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Herston
Recruitment hospital [2] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [3] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [4] 0 0
GSK Investigational Site - Fitzroy, Melbourne
Recruitment hospital [5] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [6] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
- Camperdown
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy, Melbourne
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Hawaii
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Iowa
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Massachusetts
Country [15] 0 0
United States of America
State/province [15] 0 0
Michigan
Country [16] 0 0
United States of America
State/province [16] 0 0
Missouri
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
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Ohio
Country [20] 0 0
United States of America
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Oklahoma
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Manitoba
Country [27] 0 0
Canada
State/province [27] 0 0
Nova Scotia
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Czechia
State/province [30] 0 0
Brno - Bohunice
Country [31] 0 0
Czechia
State/province [31] 0 0
Hradec Kralove
Country [32] 0 0
Czechia
State/province [32] 0 0
Praha 4
Country [33] 0 0
Czechia
State/province [33] 0 0
Praha 6
Country [34] 0 0
Germany
State/province [34] 0 0
Baden-Wuerttemberg
Country [35] 0 0
Germany
State/province [35] 0 0
Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Saarland
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Germany
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Sachsen-Anhalt
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Hamburg
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Israel
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Haifa
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Israel
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Jerusalem
Country [46] 0 0
Israel
State/province [46] 0 0
Nazareth
Country [47] 0 0
Israel
State/province [47] 0 0
Petach-Tikva
Country [48] 0 0
Israel
State/province [48] 0 0
Rehovot
Country [49] 0 0
Israel
State/province [49] 0 0
Tel-Aviv
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Daegu
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Pusan
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Seoul
Country [53] 0 0
Malaysia
State/province [53] 0 0
Bandar Tun Razak, Cheras
Country [54] 0 0
Malaysia
State/province [54] 0 0
Kepong
Country [55] 0 0
New Zealand
State/province [55] 0 0
Auckland
Country [56] 0 0
Puerto Rico
State/province [56] 0 0
San Juan
Country [57] 0 0
Romania
State/province [57] 0 0
Bucharest
Country [58] 0 0
Romania
State/province [58] 0 0
Cluj-Napoca, Cluj
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Moscow
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Saint-Petersburg
Country [61] 0 0
Singapore
State/province [61] 0 0
Singapore
Country [62] 0 0
Taiwan
State/province [62] 0 0
Kaohsiung
Country [63] 0 0
Taiwan
State/province [63] 0 0
Taipei
Country [64] 0 0
Taiwan
State/province [64] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to examine the safety and effectiveness of GI262570 compared to
placebo (a pill that looks exactly like GI262570 but contains no active medicine) in
improving specific tests that indicate the degree of liver fibrosis (scarring). Subjects who
are enrolled in the study must have had prior treatment with interferon (either pegylated or
standard interferon) plus ribavirin for at least 12 weeks to treat their hepatitis C, but
either failed to clear the virus or didn't tolerate the treatment.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00244751
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries