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

Mean Change From Baseline in Fibrosis as Quantified by Morphometric Image Analysis

时间窗: 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.

Number of Participants With Fluid Retention Events

时间窗: 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.

Mean Change From Baseline in Heart Rate

时间窗: 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.

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

时间窗: 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.

Number of Participants With Abnormal ECG Findings

时间窗: 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.

Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time

时间窗: 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.

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSP)

时间窗: 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.

Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52

时间窗: 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.

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: 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.