Antifibrotic Activity Of GI262570 In Chronic Hepatitis C Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00244751
• Collaborator: (none)
• Enrollment: 265
• Locations: 121
• Arms: 3
• Actual Duration (Months): 28.3
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis, Liver	Drug: GI262570 0.5 mg; Drug: GI262570 1.0 mg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 265 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Nov 2, 2005
• Actual Primary Completion Date: Mar 13, 2008
• Actual Study Completion Date: Mar 13, 2008

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: GI262570 0.5 mg; GI262570 0.5 mg
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.	Drug: GI262570 1.0 mg; GI262570 1.0 mg
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.	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Liver Biopsy Immunohistochemical Marker of Hepatic Stellate Cell (HSC) Activation and Collagen Synthesis at Week 52 [Baseline and Week 52]

   A percutaneous liver biopsy was obtained at the screening visit and at Week 52. A new liver biopsy at the screening visit was not taken in the event that a previous liver biopsy taken within 120 days of the Baseline /Day 1 visit (day of first dose), and the tissue block was available. The immunohistochemical marker assessed was smooth muscle alpha-actin (aSMA). Sections of the liver biopsies were stained by standard immunocytochemical techniques using a monoclonal antibody to smooth muscle actin with 'very intense purple' as the detection chromogen. This gives a reddish-purple color to the activated stellate cells, which strongly contrasts with the rest of the tissue. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing. The values are presented as proportion of positive area over total area.

2. Mean Change From Baseline in Fibrosis as Quantified by Morphometric Image Analysis [Baseline and at Week 52]

   A percutaneous liver biopsy was obtained at the screening visit and at Week 52. A new liver biopsy at the screening visit was not taken in the event that a previous liver biopsy taken within 120 days of the Baseline /Day 1 visit (day of first dose), and the tissue block was available. Morphometric analysis was performed using specimens stained with Sirius red and computerized image analysis. Sirius red was used to stain extracellular collagen in liver sections. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing. The values are presented as proportion of positive area over total area.

3. Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 [Week 52]

   In ranked assessment (fibrosis and necroinflammation), available slides from each participant were evaluated as to whether one slide presents a globally more benign histopathology or whether the matched slides comprise globally equivalent histologic patterns. Subsequent data analysis revealed whether slides scored (within matched pairs of slides) as more benign occurred in different proportions of the Week 52 liver biopsies, according to treatment group. The number of participants with paired biopsies was based on the number with a Rank Assessment.

4. Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 4 weeks post treatment (52 weeks)]

   AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

5. Number of Participants With Abnormal ECG Findings [Up to 4 weeks post-treatment (52 weeks)]

   A standardized 12-lead ECGs were recorded at pre-screening, and pre-dose, at Baseline/Day 1, Weeks 16, 34, and 52 or withdrawal and at the 4 week follow-up visit. Any conditions such as bundle branch block, repolarization, depolarization, abnormal sinus rhythms, atrial fibrillation etc. are considered to be clinically abnormal findings.

6. Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time [Up to 4 weeks post-treatment (52 weeks)]

   Clinical laboratory parameters: Alkaline phosphatase, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Total bilirubin, Cholesterol, Carbon dioxide content/Bicarbonate (CO2/HCO3), Creatinine, Glucose, Hemoglobin, Potassium, Low density lipid (LDL) cholesterol, Lymphocytes, Sodium, Segmented neutrophils, Platelet count, White blood cell (WBC) count were assessed for change in grade toxicities. Toxicities were graded as grade 1 to grade 4 in increasing order of severity of toxicity. Thus grade 4 indicating severe toxicity. Only those parameters with grade 3 and 4 toxicities are presented.

7. Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSP) [Baseline and up to 4 weeks post-treatment (52 weeks)]

   SBP and DBP readings were taken at pre-screening, pre-dose after 10 minutes of rest, at Baseline/Day 1, weeks 2, 4, 10, 16, 22, 28, 34, 40, 46, and 52 or WD and at the 4 week follow-up visit. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

8. Mean Change From Baseline in Heart Rate [Baseline and up to 4 weeks post-treatment (52 weeks)]

   Heart rate assessment were done at pre-screening, pre-dose after 10 minutes of rest, at Baseline/Day 1, weeks 2, 4, 10, 16, 22, 28, 34, 40, 46, and 52 or WD and at the 4 week follow-up visit. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to be missing.

9. Number of Participants With Fluid Retention Events [Up to 4 weeks post-treatment (52 weeks)]

   Fluid retention event was one of the AEs reported. AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Secondary Outcome Measures

1. Number of Participants Progressing at Least 1 Point on the Ishak Fibrosis Score at Week 52 [Week 52]

   Progression was defined as an increase by at least one point in the fibrosis score. Score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The number of participants with paired biopsies is based on the number with an Ishak Fibrosis score.

2. Number of Participants Regressing at Least 1 Point on the Ishak Fibrosis Score at Week 52 [Week 52]

   Regression was defined as a decrease by at least one point in the fibrosis score. Score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The number of participants with paired biopsies is based on the number with an Ishak Fibrosis score.

3. Number of Participants Whose Ishak Fibrosis Score Remains Unchanged at Week 52 [Week 52]

   No change was defined as having the same score at both Baseline and at Week 52. Score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The number of participants with paired biopsies is based on the number with an Ishak Fibrosis score.

4. Mean Change From Screening in Total Ishak Score (Necroinflammatory Score and Fibrosis Score) at Week 52 [Screening and Week 52]

   Ishak score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The necroinflammatory score is the combined score for necrosis and inflammation domains and ranged from 0 (best) to 14 (worst). Change from screening was calculated as the post screening assessment minus the screening assessment for a given parameter.

5. Mean Change From Screening in Metavir Scores at Week 52 [Screening and Week 52]

   Metavir activity score ranged from 0 to 3 (higher score indicates severe symptoms of necrosis). 0: Piecemeal necrosis (PMN) absent and lobular necrosis (LN) absent or slight, 1: PMN slight and LN moderate, 2: PMN moderate and LN severe, 3: PMN severe. Metavir fibrosis score ranged from 0 to 4 (higher score indicates severe symptoms of necrosis). 0: No fibrosis, 1: Portal fibrosis without septa, 2: Portal fibrosis with septa, 3: Septal fibrosis without cirrhosis, 4: Cirrhosis. Change from screening was calculated as the post screening assessment minus the screening assessment for a given parameter.

6. Mean Change From Baseline in Serum FibroSure (FibroTest/ActiTest) Score at Week 52 [Baseline and Week 52]

   FibroTest was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase. FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and >= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase. ActiTest was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and >= 0.61 indicates severe necrosis. Day 1 value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

7. Mean Change From Baseline in Serum ALT Levels [Baseline and Week 52]

   ALT was assessed as per upper limit of normal where the normal range was 0-48 international units per liter. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

8. Mean Change From Baseline in Measures of Insulin Resistance [Baseline and Week 52]

   Insulin resistance was measured using Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Belfiore Insulin Sensitivity Index (ISI) and Quantitative Insulin Sensitivity Check Index (QUICKI). HOMA-IR = fasting plasma insulin*fasting plasma glucose / 22.5 and ISI = 2 / [(fasting plasma glucose from the participant / fasting plasma glucose normal reference range)*( fasting plasma insulin from the participant / fasting plasma insulin normal reference range) + 1] and QUICKI = 1/(log[fasting plasma Insulin] + log[fasting plasma glucose]). Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

9. Median Change From Baseline in Serum ALT Over Time [Baseline and up to 4 weeks post-treatment (52 weeks)]

   ALT was assessed as per upper limit of normal where the normal range was 0-48 international units per liter. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

10. Mean Change From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 52 [Baseline and Week 52]

    Value at Day 1 visit (day of first dose) was considered as Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

11. Median Change From Baseline in Serum HCV RNA Levels Over Time [Baseline and up to 4 weeks post-treatment (52 weeks)]

    Serum for HCV RNA levels were collected at pre-screen, Baseline, Week 28, Week 52, and at the 4 week follow up visit. Value at Day 1 visit (day of first dose) was considered as Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.

12. Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length 'Tau' (AUC [0-tau]) of GI262570 on Week 2 [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]

    Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

13. Dose Normalized (DN) AUC (0-tau) of GI262570 on Week 2 [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]

    Sample s for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

14. Apparent Clearance Following Oral Dosing (CL/F) of GI262570 on Week 2 [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]

    Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

15. Maximum Observed Concentration (Cmax), Minimum Observed Concentration (Cmin) of GI262570 on Week 2 [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]

    Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

16. DN Cmax of GI262570 on Week 2 [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]

    Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

17. Terminal Elimination Half-life (T1/2), Time to First Quantifiable Concentration (Tlag) and Time to Cmax (Tmax) of GI262570 on Week 2 [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]

    Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

18. Volume of Distribution Expressed as a Function of Bioavailability (V/F) of GI262570 [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]

    Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.

19. GI262570 Serum Concentrations on Week 2, 16, 28, 40, and Week 52 [Weeks 2, 16, 28, 40 and 52]

    Samples for Week 2 serial group were planned to be collected 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. For Weeks 16 and 40 samples were planned to be collected at 0 (pre-morning dose)1 and between 1.5-6 hour post-morning dose 2. For Weeks 28 and 52 samples were planned to be collected at 0 (pre-morning dose)1 and between 6-10 hour post-morning dose 2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294-0005
2	GSK Investigational Site	Tucson	Arizona	United States	85719
3	GSK Investigational Site	North Little Rock	Arkansas	United States	72117
4	GSK Investigational Site	Bakersfield	California	United States	93301
5	GSK Investigational Site	La Jolla	California	United States	92024
6	GSK Investigational Site	Los Angeles	California	United States	90048
7	GSK Investigational Site	Los Angeles	California	United States	90095
8	GSK Investigational Site	Newport Beach	California	United States	92663
9	GSK Investigational Site	Pasadena	California	United States	91105
10	GSK Investigational Site	Sacramento	California	United States	95825
11	GSK Investigational Site	San Clemente	California	United States	92673
12	GSK Investigational Site	San Francisco	California	United States	94121
13	GSK Investigational Site	Santa Clara	California	United States	95051
14	GSK Investigational Site	Englewood	Colorado	United States	80113
15	GSK Investigational Site	Washington	District of Columbia	United States	20010
16	GSK Investigational Site	Fort Lauderdale	Florida	United States	33308
17	GSK Investigational Site	Miami	Florida	United States	33136
18	GSK Investigational Site	Orlando	Florida	United States	32804
19	GSK Investigational Site	Sarasota	Florida	United States	34243
20	GSK Investigational Site	Atlanta	Georgia	United States	30033
21	GSK Investigational Site	Atlanta	Georgia	United States	30308
22	GSK Investigational Site	Atlanta	Georgia	United States	30309
23	GSK Investigational Site	Marietta	Georgia	United States	30060
24	GSK Investigational Site	Honolulu	Hawaii	United States	96817
25	GSK Investigational Site	Indianapolis	Indiana	United States	46202
26	GSK Investigational Site	Iowa City	Iowa	United States	52242
27	GSK Investigational Site	Louisville	Kentucky	United States	40202
28	GSK Investigational Site	Lutherville-Timonium	Maryland	United States	21093
29	GSK Investigational Site	Boston	Massachusetts	United States	02111
30	GSK Investigational Site	Boston	Massachusetts	United States	02114
31	GSK Investigational Site	Boston	Massachusetts	United States	02215
32	GSK Investigational Site	Worcester	Massachusetts	United States	01655
33	GSK Investigational Site	Ann Arbor	Michigan	United States	48109
34	GSK Investigational Site	Detroit	Michigan	United States	48202
35	GSK Investigational Site	Saint Louis	Missouri	United States	63104
36	GSK Investigational Site	Binghamton	New York	United States	13901
37	GSK Investigational Site	Manhasset	New York	United States	11030
38	GSK Investigational Site	New York	New York	United States	10003
39	GSK Investigational Site	New York	New York	United States	10021
40	GSK Investigational Site	New York	New York	United States	10029
41	GSK Investigational Site	New York	New York	United States	10032
42	GSK Investigational Site	Syracuse	New York	United States	13210
43	GSK Investigational Site	The Bronx	New York	United States	10468
44	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599
45	GSK Investigational Site	Durham	North Carolina	United States	27710
46	GSK Investigational Site	Cincinnati	Ohio	United States	45219
47	GSK Investigational Site	Cincinnati	Ohio	United States	45267-0595
48	GSK Investigational Site	Cleveland	Ohio	United States	44195
49	GSK Investigational Site	Tulsa	Oklahoma	United States	74104
50	GSK Investigational Site	Hershey	Pennsylvania	United States	17033-0850
51	GSK Investigational Site	Lancaster	Pennsylvania	United States	17604-3200
52	GSK Investigational Site	Dallas	Texas	United States	75390-8887
53	GSK Investigational Site	Houston	Texas	United States	77030
54	GSK Investigational Site	San Antonio	Texas	United States	78215
55	GSK Investigational Site	Charlottesville	Virginia	United States	22908
56	GSK Investigational Site	Fairfax	Virginia	United States	22031
57	GSK Investigational Site	Richmond	Virginia	United States	23249
58	GSK Investigational Site	Richmond	Virginia	United States	23298
59	GSK Investigational Site	Herston	Queensland	Australia	4029
60	GSK Investigational Site	Camperdown	Victoria	Australia
61	GSK Investigational Site	Clayton	Victoria	Australia	3168
62	GSK Investigational Site	Fitzroy, Melbourne	Victoria	Australia	3065
63	GSK Investigational Site	Heidelberg	Victoria	Australia	3084
64	GSK Investigational Site	Melbourne	Victoria	Australia	3004
65	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4N1
66	GSK Investigational Site	Vancouver	British Columbia	Canada	V5Z 1H2
67	GSK Investigational Site	Victoria	British Columbia	Canada	V8V 3P9
68	GSK Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
69	GSK Investigational Site	Halifax	Nova Scotia	Canada	B3H 2Y9
70	GSK Investigational Site	London	Ontario	Canada	N6A 5A5
71	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
72	GSK Investigational Site	Toronto	Ontario	Canada	M5G 1X5
73	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2N2
74	GSK Investigational Site	Toronto	Ontario	Canada	M5T 2S8
75	GSK Investigational Site	Montreal	Quebec	Canada	H2X 3J4
76	GSK Investigational Site	Brno - Bohunice		Czechia	625 00
77	GSK Investigational Site	Hradec Kralove		Czechia	500 12
78	GSK Investigational Site	Praha 4		Czechia	140 21
79	GSK Investigational Site	Praha 6		Czechia	169 02
80	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79106
81	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
82	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
83	GSK Investigational Site	Erlangen	Bayern	Germany	91054
84	GSK Investigational Site	Frankfurt	Hessen	Germany	60590
85	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
86	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
87	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen	Germany	40225
88	GSK Investigational Site	Muenster	Nordrhein-Westfalen	Germany	48149
89	GSK Investigational Site	Homburg	Saarland	Germany	66421
90	GSK Investigational Site	Halle	Sachsen-Anhalt	Germany	06120
91	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
92	GSK Investigational Site	Berlin		Germany	13353
93	GSK Investigational Site	Hamburg		Germany	20246
94	GSK Investigational Site	Haifa		Israel	31096
95	GSK Investigational Site	Jerusalem		Israel	91120
96	GSK Investigational Site	Nazareth		Israel	16100
97	GSK Investigational Site	Petach-Tikva		Israel	49100
98	GSK Investigational Site	Rehovot		Israel	76100
99	GSK Investigational Site	Tel-Aviv		Israel	64239
100	GSK Investigational Site	Daegu		Korea, Republic of	700-721
101	GSK Investigational Site	Pusan		Korea, Republic of	602-739
102	GSK Investigational Site	Seoul		Korea, Republic of	135-710
103	GSK Investigational Site	Seoul		Korea, Republic of	138-736
104	GSK Investigational Site	Seoul		Korea, Republic of	150-713
105	GSK Investigational Site	Bandar Tun Razak, Cheras		Malaysia	59100
106	GSK Investigational Site	Kepong		Malaysia	68100
107	GSK Investigational Site	Auckland		New Zealand	1001
108	GSK Investigational Site	San Juan		Puerto Rico	00909-1711
109	GSK Investigational Site	Bucharest		Romania	021105
110	GSK Investigational Site	Bucharest		Romania	022328
111	GSK Investigational Site	Cluj-Napoca, Cluj		Romania	400162
112	GSK Investigational Site	Moscow		Russian Federation	105229
113	GSK Investigational Site	Moscow		Russian Federation	115516
114	GSK Investigational Site	Moscow		Russian Federation	121170
115	GSK Investigational Site	Moscow		Russian Federation	129110
116	GSK Investigational Site	Saint-Petersburg		Russian Federation
117	GSK Investigational Site	Singapore		Singapore	169608
118	GSK Investigational Site	Kaohsiung		Taiwan	80708
119	GSK Investigational Site	Kaohsiung		Taiwan	833
120	GSK Investigational Site	Taipei		Taiwan	112
121	GSK Investigational Site	Taoyuan		Taiwan	333

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00244751
• Other Study ID Numbers: FBX104114
• First Posted: Oct 27, 2005
• Last Update Posted: Dec 11, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by GlaxoSmithKline: Hepatitis C liver fibrosis
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Cirrhosis

Study Results

Participant Flow

Recruitment Details	The study was conducted in North America, Europe, and the International region. There were 22 study sites in Europe, 9 study sites in the International region and 45 study sites in North America. The study was conducted duration 02-November-2005 to 03-March-2008.
Pre-assignment Detail	The study consisted of a pre-screening visit (within 60 days of first dose) and a screen visit. For this study, 110 sites screened 863 participants. Of these participants, 265 were randomized.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	88	89	88
COMPLETED	72	74	78
NOT COMPLETED	16	15	10

Baseline Characteristics

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg	Total
Arm/Group Description	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.	Participants received GI262570 0.5 mg. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 1.0 mg 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.	Total of all reporting groups
Overall Participants	88	89	88	265
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.1 (5.64)	52.2 (7.25)	51.4 (5.81)	51.9 (6.27)
Sex: Female, Male (Count of Participants)
Female	35 39.8%	36 40.4%	29 33%	100 37.7%
Male	53 60.2%	53 59.6%	59 67%	165 62.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.3%	2 2.2%	3 3.4%	7 2.6%
Asian	11 12.5%	6 6.7%	7 8%	24 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 13.6%	14 15.7%	9 10.2%	35 13.2%
White	63 71.6%	67 75.3%	68 77.3%	198 74.7%
More than one race	0 0%	0 0%	1 1.1%	1 0.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Liver Biopsy Immunohistochemical Marker of Hepatic Stellate Cell (HSC) Activation and Collagen Synthesis at Week 52
Description	A percutaneous liver biopsy was obtained at the screening visit and at Week 52. A new liver biopsy at the screening visit was not taken in the event that a previous liver biopsy taken within 120 days of the Baseline /Day 1 visit (day of first dose), and the tissue block was available. The immunohistochemical marker assessed was smooth muscle alpha-actin (aSMA). Sections of the liver biopsies were stained by standard immunocytochemical techniques using a monoclonal antibody to smooth muscle actin with 'very intense purple' as the detection chromogen. This gives a reddish-purple color to the activated stellate cells, which strongly contrasts with the rest of the tissue. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing. The values are presented as proportion of positive area over total area.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat (MITT) Population consisted of all participants with chronic hepatitis C randomized, regardless of whether or not the study drug was actually taken or if the participant completed the planned duration of the study. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5mg	GI262570 1.0mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	64	71	72
Mean (Standard Deviation) [Ratio of positive area]	0.02065 (0.047620)	0.02819 (0.048160)	0.02914 (0.040948)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GI262570 0.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3608
	Comments
	Method	reduced regression model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GI262570 1.0mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3575
	Comments
	Method	reduced regression model
	Comments

2. Primary Outcome

Title	Mean Change From Baseline in Fibrosis as Quantified by Morphometric Image Analysis
Description	A percutaneous liver biopsy was obtained at the screening visit and at Week 52. A new liver biopsy at the screening visit was not taken in the event that a previous liver biopsy taken within 120 days of the Baseline /Day 1 visit (day of first dose), and the tissue block was available. Morphometric analysis was performed using specimens stained with Sirius red and computerized image analysis. Sirius red was used to stain extracellular collagen in liver sections. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing. The values are presented as proportion of positive area over total area.
Time Frame	Baseline and at Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	65	71	72
Mean (Standard Deviation) [Ratio of positive area]	0.02541 (0.058338)	0.02613 (0.055985)	0.02527 (0.060665)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GI262570 0.5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9157
	Comments
	Method	reduced regression model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GI262570 1.0mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9501
	Comments
	Method	reduced regression model
	Comments

3. Primary Outcome

Title	Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52
Description	In ranked assessment (fibrosis and necroinflammation), available slides from each participant were evaluated as to whether one slide presents a globally more benign histopathology or whether the matched slides comprise globally equivalent histologic patterns. Subsequent data analysis revealed whether slides scored (within matched pairs of slides) as more benign occurred in different proportions of the Week 52 liver biopsies, according to treatment group. The number of participants with paired biopsies was based on the number with a Rank Assessment.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants with paired biopsies at the indicated time point were analyzed.

Arm/Group Title	Placebo	GI262570 0.5mg	GI262570 1.0mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	65	72	72
Fibrosis, better than screening	13 14.8%	17 19.1%	11 12.5%
Fibrosis, same as screening	35 39.8%	38 42.7%	35 39.8%
Fibrosis, worse than screening	16 18.2%	17 19.1%	25 28.4%
Fibrosis, missing	1 1.1%	0 0%	1 1.1%
Necrosis, better than screening	11 12.5%	20 22.5%	27 30.7%
Necrosis, same as screening	23 26.1%	24 27%	23 26.1%
Necrosis, worse than screening	31 35.2%	28 31.5%	22 25%
Necrosis, missing	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GI262570 0.5mg, GI262570 1.0mg
	Comments	Comparison for Ranked assessment (fibrosis)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6483
	Comments
	Method	Cochran-Mantel-Haenszel Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GI262570 0.5mg, GI262570 1.0mg
	Comments	Comparison for Ranked assessment (necrosis)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1776
	Comments
	Method	Cochran-Mantel-Haenszel Test
	Comments

4. Primary Outcome

Title	Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Time Frame	Up to 4 weeks post treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

As Treated Population consisted of all participants for whom no clear evidence was available of failure to take study medication.

Arm/Group Title	Placebo	GI262570 0.5mg	GI262570 1.0mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Any AE	75 85.2%	68 76.4%	71 80.7%
Any SAE	7 8%	10 11.2%	6 6.8%

5. Primary Outcome

Title	Number of Participants With Abnormal ECG Findings
Description	A standardized 12-lead ECGs were recorded at pre-screening, and pre-dose, at Baseline/Day 1, Weeks 16, 34, and 52 or withdrawal and at the 4 week follow-up visit. Any conditions such as bundle branch block, repolarization, depolarization, abnormal sinus rhythms, atrial fibrillation etc. are considered to be clinically abnormal findings.
Time Frame	Up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

As Treated Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5mg	GI262570 1.0mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Baseline, Abnormal, not clinically significant	25 28.4%	25 28.1%	22 25%
Week 16, Abnormal, not clinically significant	18 20.5%	16 18%	21 23.9%
Week 34, Abnormal, not clinically significant	12 13.6%	19 21.3%	23 26.1%
Week 34, Abnormal, clinically significant	0 0%	0 0%	1 1.1%
Week 52, Abnormal, not clinically significant	10 11.4%	18 20.2%	22 25%

6. Primary Outcome

Title	Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time
Description	Clinical laboratory parameters: Alkaline phosphatase, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Total bilirubin, Cholesterol, Carbon dioxide content/Bicarbonate (CO2/HCO3), Creatinine, Glucose, Hemoglobin, Potassium, Low density lipid (LDL) cholesterol, Lymphocytes, Sodium, Segmented neutrophils, Platelet count, White blood cell (WBC) count were assessed for change in grade toxicities. Toxicities were graded as grade 1 to grade 4 in increasing order of severity of toxicity. Thus grade 4 indicating severe toxicity. Only those parameters with grade 3 and 4 toxicities are presented.
Time Frame	Up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

As Treated Population. Only those participants available at the specified time points for particular parameter were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
ALT, grade 3	4 4.5%	2 2.2%	5 5.7%
ALT, grade 4	1 1.1%	0 0%	0 0%
AST, grade 3	4 4.5%	2 2.2%	2 2.3%
AST, grade 4	1 1.1%	0 0%	0 0%
Total bilirubin, grade 4	12 13.6%	17 19.1%	22 25%
Glucose, grade 3	1 1.1%	0 0%	0 0%
Glucose, grade 4	0 0%	1 1.1%	0 0%
Hemaglobin, grade 3	1 1.1%	1 1.1%
Potassium, grade 4	1 1.1%	0 0%	0 0%
Sodium, grade 4	1 1.1%	1 1.1%	1 1.1%
Segmented neutrophils, grade 4	1 1.1%	0 0%	0 0%
Platelet count, grade 4	1 1.1%	0 0%	0 0%

7. Primary Outcome

Title	Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSP)
Description	SBP and DBP readings were taken at pre-screening, pre-dose after 10 minutes of rest, at Baseline/Day 1, weeks 2, 4, 10, 16, 22, 28, 34, 40, 46, and 52 or WD and at the 4 week follow-up visit. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

As Treated Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
DBP, Week 2	-0.06 (12.347)	0.60 (9.129)	0.17 (8.171)
DBP, Week 4	1.12 (8.793)	-1.31 (7.560)	-0.02 (8.018)
DBP, Week 10	0.94 (9.195)	-1.62 (10.032)	0.00 (7.309)
DBP, Week 16	0.31 (9.194)	-2.00 (9.664)	0.06 (8.226)
DBP, Week 22	1.18 (10.264)	-2.46 (9.648)	0.93 (8.194)
DBP, Week 28	0.87 (10.529)	-1.09 (9.664)	0.15 (9.231)
DBP, Week 34	0.40 (11.480)	-1.38 (9.242)	0.70 (8.612)
DBP, Week 40	0.05 (10.136)	-2.20 (8.947)	1.16 (9.302)
DBP, Week 46	0.95 (10.620)	-1.16 (9.203)	1.29 (8.423)
DBP, Week 52	-0.01 (10.177)	-0.64 (9.807)	-0.13 (6.855)
DBP, Withdrawal	2.45 (9.015)	0.89 (8.852)	1.00 (5.933)
DBP, post-treatment	0.66 (11.085)	-0.29 (10.860)	0.49 (9.634)
SBP, Week 2	0.17 (16.700)	-0.53 (14.095)	0.49 (12.516)
SBP, Week 4	0.78 (16.821)	-1.34 (13.333)	-0.80 (12.343)
SBP, Week 10	2.95 (16.888)	-0.47 (14.524)	-0.85 (13.293)
SBP, Week 16	0.83 (15.621)	-1.79 (15.496)	0.10 (11.008)
SBP, Week 22	0.45 (18.161)	-1.79 (14.361)	0.59 (12.217)
SBP, Week 28	-1.82 (20.285)	-2.16 (15.260)	1.69 (14.782)
SBP, Week 34	0.95 (19.558)	-1.86 (15.059)	0.32 (13.569)
SBP, Week 40	-1.34 (19.616)	-1.04 (13.085)	-1.23 (14.371)
SBP, Week 46	-0.53 (15.173)	-1.85 (12.158)	0.30 (13.670)
SBP, Week 52	0.15 (18.950)	1.92 (13.352)	-0.21 (12.414)
SBP, Withdrawal	5.09 (25.126)	-0.44 (21.830)	-0.17 (3.488)
SBP, Post-treatment	0.25 (21.747)	1.69 (13.431)	3.52 (16.931)

8. Primary Outcome

Title	Mean Change From Baseline in Heart Rate
Description	Heart rate assessment were done at pre-screening, pre-dose after 10 minutes of rest, at Baseline/Day 1, weeks 2, 4, 10, 16, 22, 28, 34, 40, 46, and 52 or WD and at the 4 week follow-up visit. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to be missing.
Time Frame	Baseline and up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

As treated population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Week 2	1.08 (8.763)	-1.92 (7.143)	-0.28 (8.554)
Week 4	0.35 (9.726)	0.55 (10.223)	1.80 (10.221)
Week 10	2.04 (8.824)	0.49 (8.771)	0.83 (8.747)
Week 16	-0.44 (8.425)	-0.33 (9.295)	0.55 (11.070)
Week 22	2.23 (9.120)	-0.10 (10.706)	3.23 (12.141)
Week 28	0.80 (8.857)	-1.54 (8.530)	0.05 (8.237)
Week 34	0.89 (9.983)	0.77 (9.485)	-0.13 (10.655)
Week 40	-0.11 (8.340)	-1.89 (9.169)	0.09 (11.101)
Week 46	1.18 (9.411)	-1.01 (10.360)	1.08 (12.056)
Week 52	1.04 (9.300)	-0.26 (9.656)	-2.09 (12.197)
Withdrawal	5.27 (14.107)	1.00 (12.062)	-1.17 (3.061)
Post-treatment	1.20 (10.184)	-0.42 (10.287)	0.15 (11.340)

9. Primary Outcome

Title	Number of Participants With Fluid Retention Events
Description	Fluid retention event was one of the AEs reported. AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

As Treated Population.

Arm/Group Title	Placebo	GI262570 0.5mg	GI262570 1.0mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Count of Participants [Participants]	0 0%	1 1.1%	1 1.1%

10. Secondary Outcome

Title	Number of Participants Progressing at Least 1 Point on the Ishak Fibrosis Score at Week 52
Description	Progression was defined as an increase by at least one point in the fibrosis score. Score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The number of participants with paired biopsies is based on the number with an Ishak Fibrosis score.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

MITT Population.

Arm/Group Title	Placebo	GI262570 0.5mg	GI262570 1.0mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.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.
Measure Participants	64	72	71
Count of Participants [Participants]	12 13.6%	14 15.7%	19 21.6%

11. Secondary Outcome

Title	Number of Participants Regressing at Least 1 Point on the Ishak Fibrosis Score at Week 52
Description	Regression was defined as a decrease by at least one point in the fibrosis score. Score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The number of participants with paired biopsies is based on the number with an Ishak Fibrosis score.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

MITT Population.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	64	72	71
Count of Participants [Participants]	11 12.5%	14 15.7%	9 10.2%

12. Secondary Outcome

Title	Number of Participants Whose Ishak Fibrosis Score Remains Unchanged at Week 52
Description	No change was defined as having the same score at both Baseline and at Week 52. Score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The number of participants with paired biopsies is based on the number with an Ishak Fibrosis score.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

MITT Population.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	64	72	71
Count of Participants [Participants]	41 46.6%	44 49.4%	43 48.9%

13. Secondary Outcome

Title	Mean Change From Screening in Total Ishak Score (Necroinflammatory Score and Fibrosis Score) at Week 52
Description	Ishak score ranged from 0 to 6 (higher score indicates greater fibrosis). 0: No fibrosis, 1: Fibrous expansion of some portal areas, with or without short fibrous septa, 2: Fibrous expansion of most portal areas, with or without short fibrous septa, 3: Fibrous expansion of most portal areas with portal to portal bridging, 4: Fibrous expansion of portal areas with marked bridging, 5: Marked bridging with occasional nodules (incomplete cirrhosis), 6: Cirrhosis, probable or definite. The necroinflammatory score is the combined score for necrosis and inflammation domains and ranged from 0 (best) to 14 (worst). Change from screening was calculated as the post screening assessment minus the screening assessment for a given parameter.
Time Frame	Screening and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants available at the specified time point were analyzed

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Necroinflammatory Score	0.7 (1.31)	0.2 (1.60)	-0.2 (1.69)
Fibrosis Score	0.1 (0.71)	0.0 (0.85)	0.2 (0.70)

14. Secondary Outcome

Title	Mean Change From Screening in Metavir Scores at Week 52
Description	Metavir activity score ranged from 0 to 3 (higher score indicates severe symptoms of necrosis). 0: Piecemeal necrosis (PMN) absent and lobular necrosis (LN) absent or slight, 1: PMN slight and LN moderate, 2: PMN moderate and LN severe, 3: PMN severe. Metavir fibrosis score ranged from 0 to 4 (higher score indicates severe symptoms of necrosis). 0: No fibrosis, 1: Portal fibrosis without septa, 2: Portal fibrosis with septa, 3: Septal fibrosis without cirrhosis, 4: Cirrhosis. Change from screening was calculated as the post screening assessment minus the screening assessment for a given parameter.
Time Frame	Screening and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Metavir: Activity	0.18 (0.556)	-0.01 (0.722)	-0.04 (0.680)
Metavir: Fibrosis	0.02 (0.604)	0.04 (0.777)	0.13 (0.653)

15. Secondary Outcome

Title	Mean Change From Baseline in Serum FibroSure (FibroTest/ActiTest) Score at Week 52
Description	FibroTest was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase. FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and >= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase. ActiTest was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and >= 0.61 indicates severe necrosis. Day 1 value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	81	80	78
FibroSure: Fibrosis Score	-0.004 (0.2187)	-0.064 (0.3032)	-0.103 (0.3044)
FibroSure: Activity Score	-0.010 (0.1669)	-0.069 (0.2899)	-0.132 (0.2855)

16. Secondary Outcome

Title	Mean Change From Baseline in Serum ALT Levels
Description	ALT was assessed as per upper limit of normal where the normal range was 0-48 international units per liter. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	83	83	80
Mean (Standard Deviation) [Per upper limit normal]	0.085 (0.8028)	-0.031 (0.6004)	-0.377 (1.0743)

17. Secondary Outcome

Title	Mean Change From Baseline in Measures of Insulin Resistance
Description	Insulin resistance was measured using Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Belfiore Insulin Sensitivity Index (ISI) and Quantitative Insulin Sensitivity Check Index (QUICKI). HOMA-IR = fasting plasma insulin*fasting plasma glucose / 22.5 and ISI = 2 / [(fasting plasma glucose from the participant / fasting plasma glucose normal reference range)*( fasting plasma insulin from the participant / fasting plasma insulin normal reference range) + 1] and QUICKI = 1/(log[fasting plasma Insulin] + log[fasting plasma glucose]). Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

As Treated Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	60	65	64
HOMA-IR	0.9743 (6.28858)	-1.3027 (4.73127)	-1.8585 (3.95012)
QUICKI	-0.0022 (0.01139)	0.0029 (0.01311)	0.0070 (0.01106)
ISI	-0.0451 (0.24469)	0.0718 (0.28736)	0.1601 (0.24878)

18. Secondary Outcome

Title	Median Change From Baseline in Serum ALT Over Time
Description	ALT was assessed as per upper limit of normal where the normal range was 0-48 international units per liter. Day 1 (before dosing) value was considered to be as Baseline value. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Week 2	-0.021	-0.083	-0.167
Week 4	-0.042	-0.063	-0.167
Week 10	-0.021	-0.063	-0.219
Week 16	0.021	-0.125	-0.208
Week 22	0.010	-0.146	-0.198
Week 28	-0.021	-0.146	-0.208
Week 34	-0.042	-0.188	-0.271
Week 40	-0.021	-0.104	-0.208
Week 46	-0.063	-0.146	-0.229
Week 52	0.021	-0.083	-0.271
Post-treatment	-0.042	-0.146	-0.229

19. Secondary Outcome

Title	Mean Change From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 52
Description	Value at Day 1 visit (day of first dose) was considered as Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	82	78	82
Mean (Standard Deviation) [Log10 International unit per milliliter]	-0.020 (0.4264)	-0.006 (0.3760)	0.040 (0.4803)

20. Secondary Outcome

Title	Median Change From Baseline in Serum HCV RNA Levels Over Time
Description	Serum for HCV RNA levels were collected at pre-screen, Baseline, Week 28, Week 52, and at the 4 week follow up visit. Value at Day 1 visit (day of first dose) was considered as Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment for a given parameter. If either the Baseline or on-treatment value was missing, the change from Baseline value was also set to missing.
Time Frame	Baseline and up to 4 weeks post-treatment (52 weeks)

Outcome Measure Data

Analysis Population Description

MITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	GI262570 0.5 mg	GI262570 1.0 mg
Arm/Group Description	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.	Participants received GI262570 0.5 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.	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.
Measure Participants	88	89	88
Week 28	0.112	0.011	0.071
Week 52	-0.059	0.034	0.013
Post-treatment	0.024	0.039	0.026

21. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length 'Tau' (AUC [0-tau]) of GI262570 on Week 2
Description	Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) Parameter Population included all participants in the subset having the serial PK profiles performed at Week 2 and having sufficient data for the calculation of the PK parameters. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
Geometric Mean (Geometric Coefficient of Variation) [Hour nanograms per milliliter]	68.65 (64)	88.87 (34)	151.11 (55)	141.03 (29)

22. Secondary Outcome

Title	Dose Normalized (DN) AUC (0-tau) of GI262570 on Week 2
Description	Sample s for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started it receiving once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started it receiving once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
Geometric Mean (Geometric Coefficient of Variation) [Hours nanograms per milliliter per mg]	68.65 (64)	88.87 (34)	75.55 (55)	70.52 (29)

23. Secondary Outcome

Title	Apparent Clearance Following Oral Dosing (CL/F) of GI262570 on Week 2
Description	Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
Geometric Mean (Geometric Coefficient of Variation) [milliliter per hour]	7283.04 (64)	5626.48 (34)	6617.76 (55)	7090.62 (29)

24. Secondary Outcome

Title	Maximum Observed Concentration (Cmax), Minimum Observed Concentration (Cmin) of GI262570 on Week 2
Description	Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
Cmax	21.10 (61)	30.30 (28)	49.60 (47)	50.38 (26)
Cmin	0.69 (139)	0.19 (72)	1.54 (86)	0.18 (65)

25. Secondary Outcome

Title	DN Cmax of GI262570 on Week 2
Description	Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started it receiving once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started it receiving once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter per mg]	21.10 (61)	30.30 (28)	24.80 (47)	25.19 (26)

26. Secondary Outcome

Title	Terminal Elimination Half-life (T1/2), Time to First Quantifiable Concentration (Tlag) and Time to Cmax (Tmax) of GI262570 on Week 2
Description	Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
T1/2	3.33	2.47	2.54	2.25
Tlag	0.000	0.000	0.000	0.000
Tmax	2.00	1.50	1.75	1.75

27. Secondary Outcome

Title	Volume of Distribution Expressed as a Function of Bioavailability (V/F) of GI262570
Description	Samples for Week 2 serial group were collected 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. Initially the doses selected for the study were 0.5 mg twice daily and 1.0 mg twice daily. However, because of implementation of Amendment 4, the dose regimen was reduced to half the original dosing resulting in dose once daily.
Time Frame	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

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	8	19	8	14
Geometric Mean (Geometric Coefficient of Variation) [milliliter]	33440.98 (83)	19971.49 (51)	25616.42 (85)	24355.48 (52)

28. Secondary Outcome

Title	GI262570 Serum Concentrations on Week 2, 16, 28, 40, and Week 52
Description	Samples for Week 2 serial group were planned to be collected 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. For Weeks 16 and 40 samples were planned to be collected at 0 (pre-morning dose)1 and between 1.5-6 hour post-morning dose 2. For Weeks 28 and 52 samples were planned to be collected at 0 (pre-morning dose)1 and between 6-10 hour post-morning dose 2.
Time Frame	Weeks 2, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

PK parameter Population. Initially the doses selected were twice daily, but after implementation of Amendment 4 the dose regimen was reduced to half the original dosing. Data was not collected for this endpoint.

Arm/Group Title	GI262570 0.5 mg Twice Daily	GI262570 0.5 mg Once Daily	GI262570 1.0 mg Twice Daily	GI262570 1.0 mg Once Daily
Arm/Group Description	Participants in this arm received GI262570 0.5 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	Participants received GI262570 0.5 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.	Participants in this arm received GI262570 1.0 mg tablet twice daily as per protocol amendment 3. After implementation of protocol 4, they started receiving it once daily. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	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.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	AEs were collected from start of study medication through treatment phase (52 weeks) and assessed up to 56 weeks (4 weeks follow up). SAEs were collected from pre-screening (within 60 days of first dose up to follow up.
Adverse Event Reporting Description	AEs and SAEs were reported for the As treated Population which consisted of all participants for whom no clear evidence was available of failure to take study medication.
Arm/Group Title	Placebo		GI262570 0.5 mg		GI262570 1.0 mg
Arm/Group Description	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.		Participants received GI262570 0.5 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.		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.
All Cause Mortality
	Placebo		GI262570 0.5 mg		GI262570 1.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/88 (0%)		0/89 (0%)		0/88 (0%)
Serious Adverse Events
	Placebo		GI262570 0.5 mg		GI262570 1.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/88 (8%)		10/89 (11.2%)		6/88 (6.8%)
Blood and lymphatic system disorders
Pancytopenia	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Cardiac disorders
Cardiac failure congestive	0/88 (0%)		0/89 (0%)		1/88 (1.1%)
Myocardial ischaemia	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Ear and labyrinth disorders
Vertigo positional	0/88 (0%)		0/89 (0%)		1/88 (1.1%)
Gastrointestinal disorders
Colitis erosive	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Oesophageal obstruction	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
General disorders
Chest pain	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Fatigue	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Hepatobiliary disorders
Cholelithiasis	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Haemobilia	0/88 (0%)		0/89 (0%)		1/88 (1.1%)
Jaundice	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Infections and infestations
Abscess intestinal	0/88 (0%)		0/89 (0%)		1/88 (1.1%)
Cellulitis	0/88 (0%)		0/89 (0%)		1/88 (1.1%)
Injury, poisoning and procedural complications
Road traffic accident	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Metabolism and nutrition disorders
Hyponatraemia	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Colon neoplasm	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Pelvic neoplasm	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Prostate cancer	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Nervous system disorders
Syncope	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Psychiatric disorders
Alcohol abuse	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Bipolar disorder	0/88 (0%)		1/89 (1.1%)		0/88 (0%)
Renal and urinary disorders
Urethral stenosis	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Vascular disorders
Aortic stenosis	0/88 (0%)		0/89 (0%)		1/88 (1.1%)
Vasculitis	1/88 (1.1%)		0/89 (0%)		0/88 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		GI262570 0.5 mg		GI262570 1.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/88 (65.9%)		50/89 (56.2%)		55/88 (62.5%)
Gastrointestinal disorders
Diarrhoea	3/88 (3.4%)		10/89 (11.2%)		4/88 (4.5%)
Nausea	7/88 (8%)		3/89 (3.4%)		6/88 (6.8%)
Abdominal pain	5/88 (5.7%)		4/89 (4.5%)		4/88 (4.5%)
Abdominal pain upper	6/88 (6.8%)		5/89 (5.6%)		2/88 (2.3%)
Constipation	5/88 (5.7%)		3/89 (3.4%)		5/88 (5.7%)
Abdominal distension	2/88 (2.3%)		5/89 (5.6%)		3/88 (3.4%)
General disorders
Fatigue	14/88 (15.9%)		15/89 (16.9%)		10/88 (11.4%)
Oedema peripheral	13/88 (14.8%)		6/89 (6.7%)		9/88 (10.2%)
Infections and infestations
Nasopharyngitis	3/88 (3.4%)		5/89 (5.6%)		8/88 (9.1%)
Upper respiratory tract infection	5/88 (5.7%)		3/89 (3.4%)		5/88 (5.7%)
Urinary tract infection	5/88 (5.7%)		2/89 (2.2%)		1/88 (1.1%)
Investigations
Weight increased	13/88 (14.8%)		17/89 (19.1%)		16/88 (18.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/88 (8%)		4/89 (4.5%)		6/88 (6.8%)
Back pain	5/88 (5.7%)		5/89 (5.6%)		5/88 (5.7%)
Nervous system disorders
Headache	8/88 (9.1%)		9/89 (10.1%)		6/88 (6.8%)
Dizziness	2/88 (2.3%)		5/89 (5.6%)		10/88 (11.4%)
Psychiatric disorders
Insomnia	5/88 (5.7%)		5/89 (5.6%)		6/88 (6.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	6/88 (6.8%)		5/89 (5.6%)		4/88 (4.5%)
Skin and subcutaneous tissue disorders
Rash	4/88 (4.5%)		7/89 (7.9%)		2/88 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.