Trial Outcomes & Findings for Antifibrotic Activity Of GI262570 In Chronic Hepatitis C Subjects (NCT NCT00244751)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

265 participants

Primary outcome timeframe

Baseline and Week 52

Results posted on

2017-12-11

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	88	89	88
Overall Study COMPLETED	72	74	78
Overall Study NOT COMPLETED	16	15	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Adverse Event	7	7	5
Overall Study Lost to Follow-up	0	1	0
Overall Study Protocol Violation	1	0	1
Overall Study Withdrawal by Subject	7	5	3
Overall Study Elevated liver enzymes	1	0	0
Overall Study Lack of compliance with protocol	0	1	0
Overall Study Safety reasons	0	1	0
Overall Study Participant randomized by mistake	0	0	1

Baseline Characteristics

Antifibrotic Activity Of GI262570 In Chronic Hepatitis C Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=88 Participants 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.	GI262570 0.5 mg n=89 Participants Participants received GI262570 0.5 mg. Participant received their morning dose at the site on Weeks 2, 16, 28, 40, and 52.	GI262570 1.0 mg n=88 Participants 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 n=265 Participants Total of all reporting groups
Age, Continuous	52.1 Years STANDARD_DEVIATION 5.64 • n=5 Participants	52.2 Years STANDARD_DEVIATION 7.25 • n=7 Participants	51.4 Years STANDARD_DEVIATION 5.81 • n=5 Participants	51.9 Years STANDARD_DEVIATION 6.27 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	36 Participants n=7 Participants	29 Participants n=5 Participants	100 Participants n=4 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	53 Participants n=7 Participants	59 Participants n=5 Participants	165 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	14 Participants n=7 Participants	9 Participants n=5 Participants	35 Participants n=4 Participants
Race (NIH/OMB) White	63 Participants n=5 Participants	67 Participants n=7 Participants	68 Participants n=5 Participants	198 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants 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.	GI262570 0.5mg n=71 Participants 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.	GI262570 1.0mg n=72 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Liver Biopsy Immunohistochemical Marker of Hepatic Stellate Cell (HSC) Activation and Collagen Synthesis at Week 52	0.02065 Ratio of positive area Standard Deviation 0.047620	0.02819 Ratio of positive area Standard Deviation 0.048160	0.02914 Ratio of positive area Standard Deviation 0.040948	—

PRIMARY outcome

Timeframe: Baseline and at Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants 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.	GI262570 0.5mg n=71 Participants 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.	GI262570 1.0mg n=72 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Fibrosis as Quantified by Morphometric Image Analysis	0.02541 Ratio of positive area Standard Deviation 0.058338	0.02613 Ratio of positive area Standard Deviation 0.055985	0.02527 Ratio of positive area Standard Deviation 0.060665	—

PRIMARY outcome

Timeframe: Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants 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.	GI262570 0.5mg n=72 Participants 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.	GI262570 1.0mg n=72 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Fibrosis, same as screening	35 Participants	38 Participants	35 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Fibrosis, better than screening	13 Participants	17 Participants	11 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Fibrosis, worse than screening	16 Participants	17 Participants	25 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Fibrosis, missing	1 Participants	0 Participants	1 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Necrosis, better than screening	11 Participants	20 Participants	27 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Necrosis, same as screening	23 Participants	24 Participants	23 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Necrosis, worse than screening	31 Participants	28 Participants	22 Participants	—
Number of Participants With Ranked Histological Assessment of the Paired Biopsies at Week 52 Necrosis, missing	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to 4 weeks post treatment (52 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	75 Participants	68 Participants	71 Participants	—
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	7 Participants	10 Participants	6 Participants	—

PRIMARY outcome

Timeframe: Up to 4 weeks post-treatment (52 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants With Abnormal ECG Findings Week 52, Abnormal, not clinically significant	10 Participants	18 Participants	22 Participants	—
Number of Participants With Abnormal ECG Findings Baseline, Abnormal, not clinically significant	25 Participants	25 Participants	22 Participants	—
Number of Participants With Abnormal ECG Findings Week 16, Abnormal, not clinically significant	18 Participants	16 Participants	21 Participants	—
Number of Participants With Abnormal ECG Findings Week 34, Abnormal, not clinically significant	12 Participants	19 Participants	23 Participants	—
Number of Participants With Abnormal ECG Findings Week 34, Abnormal, clinically significant	0 Participants	0 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to 4 weeks post-treatment (52 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time ALT, grade 3	4 Participants	2 Participants	5 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time ALT, grade 4	1 Participants	0 Participants	0 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time AST, grade 3	4 Participants	2 Participants	2 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time AST, grade 4	1 Participants	0 Participants	0 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Total bilirubin, grade 4	12 Participants	17 Participants	22 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Glucose, grade 3	1 Participants	0 Participants	0 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Glucose, grade 4	0 Participants	1 Participants	0 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Hemaglobin, grade 3	—	1 Participants	1 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Potassium, grade 4	1 Participants	0 Participants	0 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Sodium, grade 4	1 Participants	1 Participants	1 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Segmented neutrophils, grade 4	1 Participants	0 Participants	0 Participants	—
Number of Participants With Change in Toxicities Grades 3 and 4 of Laboratory Parameters Over Time Platelet count, grade 4	1 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline and up to 4 weeks post-treatment (52 weeks)

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

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.

Outcome measures

PRIMARY outcome

Timeframe: Baseline and up to 4 weeks post-treatment (52 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Heart Rate Week 2	1.08 beats per minute Standard Deviation 8.763	-1.92 beats per minute Standard Deviation 7.143	-0.28 beats per minute Standard Deviation 8.554	—
Mean Change From Baseline in Heart Rate Week 34	0.89 beats per minute Standard Deviation 9.983	0.77 beats per minute Standard Deviation 9.485	-0.13 beats per minute Standard Deviation 10.655	—
Mean Change From Baseline in Heart Rate Week 40	-0.11 beats per minute Standard Deviation 8.340	-1.89 beats per minute Standard Deviation 9.169	0.09 beats per minute Standard Deviation 11.101	—
Mean Change From Baseline in Heart Rate Week 52	1.04 beats per minute Standard Deviation 9.300	-0.26 beats per minute Standard Deviation 9.656	-2.09 beats per minute Standard Deviation 12.197	—
Mean Change From Baseline in Heart Rate Post-treatment	1.20 beats per minute Standard Deviation 10.184	-0.42 beats per minute Standard Deviation 10.287	0.15 beats per minute Standard Deviation 11.340	—
Mean Change From Baseline in Heart Rate Week 46	1.18 beats per minute Standard Deviation 9.411	-1.01 beats per minute Standard Deviation 10.360	1.08 beats per minute Standard Deviation 12.056	—
Mean Change From Baseline in Heart Rate Withdrawal	5.27 beats per minute Standard Deviation 14.107	1.00 beats per minute Standard Deviation 12.062	-1.17 beats per minute Standard Deviation 3.061	—
Mean Change From Baseline in Heart Rate Week 4	0.35 beats per minute Standard Deviation 9.726	0.55 beats per minute Standard Deviation 10.223	1.80 beats per minute Standard Deviation 10.221	—
Mean Change From Baseline in Heart Rate Week 10	2.04 beats per minute Standard Deviation 8.824	0.49 beats per minute Standard Deviation 8.771	0.83 beats per minute Standard Deviation 8.747	—
Mean Change From Baseline in Heart Rate Week 16	-0.44 beats per minute Standard Deviation 8.425	-0.33 beats per minute Standard Deviation 9.295	0.55 beats per minute Standard Deviation 11.070	—
Mean Change From Baseline in Heart Rate Week 22	2.23 beats per minute Standard Deviation 9.120	-0.10 beats per minute Standard Deviation 10.706	3.23 beats per minute Standard Deviation 12.141	—
Mean Change From Baseline in Heart Rate Week 28	0.80 beats per minute Standard Deviation 8.857	-1.54 beats per minute Standard Deviation 8.530	0.05 beats per minute Standard Deviation 8.237	—

PRIMARY outcome

Timeframe: Up to 4 weeks post-treatment (52 weeks)

Population: As Treated Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants With Fluid Retention Events	0 Participants	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Week 52

Population: MITT Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants 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.	GI262570 0.5mg n=72 Participants 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.	GI262570 1.0mg n=71 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants Progressing at Least 1 Point on the Ishak Fibrosis Score at Week 52	12 Participants	14 Participants	19 Participants	—

SECONDARY outcome

Timeframe: Week 52

Population: MITT Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants 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.	GI262570 0.5mg n=72 Participants 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.	GI262570 1.0mg n=71 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants Regressing at Least 1 Point on the Ishak Fibrosis Score at Week 52	11 Participants	14 Participants	9 Participants	—

SECONDARY outcome

Timeframe: Week 52

Population: MITT Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants 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.	GI262570 0.5mg n=72 Participants 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.	GI262570 1.0mg n=71 Participants 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.	GI262570 1.0 mg Once Daily 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.
Number of Participants Whose Ishak Fibrosis Score Remains Unchanged at Week 52	41 Participants	44 Participants	43 Participants	—

SECONDARY outcome

Timeframe: Screening and Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Screening in Total Ishak Score (Necroinflammatory Score and Fibrosis Score) at Week 52 Necroinflammatory Score	0.7 Scores on a scale Standard Deviation 1.31	0.2 Scores on a scale Standard Deviation 1.60	-0.2 Scores on a scale Standard Deviation 1.69	—
Mean Change From Screening in Total Ishak Score (Necroinflammatory Score and Fibrosis Score) at Week 52 Fibrosis Score	0.1 Scores on a scale Standard Deviation 0.71	0.0 Scores on a scale Standard Deviation 0.85	0.2 Scores on a scale Standard Deviation 0.70	—

SECONDARY outcome

Timeframe: Screening and Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Screening in Metavir Scores at Week 52 Metavir: Activity	0.18 Scores on a scale Standard Deviation 0.556	-0.01 Scores on a scale Standard Deviation 0.722	-0.04 Scores on a scale Standard Deviation 0.680	—
Mean Change From Screening in Metavir Scores at Week 52 Metavir: Fibrosis	0.02 Scores on a scale Standard Deviation 0.604	0.04 Scores on a scale Standard Deviation 0.777	0.13 Scores on a scale Standard Deviation 0.653	—

SECONDARY outcome

Timeframe: Baseline and Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants 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.	GI262570 0.5mg n=80 Participants 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.	GI262570 1.0mg n=78 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Serum FibroSure (FibroTest/ActiTest) Score at Week 52 FibroSure: Fibrosis Score	-0.004 Scores on a scale Standard Deviation 0.2187	-0.064 Scores on a scale Standard Deviation 0.3032	-0.103 Scores on a scale Standard Deviation 0.3044	—
Mean Change From Baseline in Serum FibroSure (FibroTest/ActiTest) Score at Week 52 FibroSure: Activity Score	-0.010 Scores on a scale Standard Deviation 0.1669	-0.069 Scores on a scale Standard Deviation 0.2899	-0.132 Scores on a scale Standard Deviation 0.2855	—

SECONDARY outcome

Timeframe: Baseline and Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants 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.	GI262570 0.5mg n=83 Participants 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.	GI262570 1.0mg n=80 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Serum ALT Levels	0.085 Per upper limit normal Standard Deviation 0.8028	-0.031 Per upper limit normal Standard Deviation 0.6004	-0.377 Per upper limit normal Standard Deviation 1.0743	—

SECONDARY outcome

Timeframe: Baseline and Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants 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.	GI262570 0.5mg n=65 Participants 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.	GI262570 1.0mg n=64 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Measures of Insulin Resistance HOMA-IR	0.9743 Units on a scale Standard Deviation 6.28858	-1.3027 Units on a scale Standard Deviation 4.73127	-1.8585 Units on a scale Standard Deviation 3.95012	—
Mean Change From Baseline in Measures of Insulin Resistance QUICKI	-0.0022 Units on a scale Standard Deviation 0.01139	0.0029 Units on a scale Standard Deviation 0.01311	0.0070 Units on a scale Standard Deviation 0.01106	—
Mean Change From Baseline in Measures of Insulin Resistance ISI	-0.0451 Units on a scale Standard Deviation 0.24469	0.0718 Units on a scale Standard Deviation 0.28736	0.1601 Units on a scale Standard Deviation 0.24878	—

SECONDARY outcome

Timeframe: Baseline and up to 4 weeks post-treatment (52 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Median Change From Baseline in Serum ALT Over Time Week 2	-0.021 Per upper limit normal Interval -1.063 to 0.833	-0.083 Per upper limit normal Interval -1.688 to 0.854	-0.167 Per upper limit normal Interval -3.458 to 1.458	—
Median Change From Baseline in Serum ALT Over Time Week 4	-0.042 Per upper limit normal Interval -1.792 to 1.625	-0.063 Per upper limit normal Interval -2.125 to 0.917	-0.167 Per upper limit normal Interval -5.292 to 1.646	—
Median Change From Baseline in Serum ALT Over Time Week 10	-0.021 Per upper limit normal Interval -1.0 to 1.25	-0.063 Per upper limit normal Interval -1.271 to 1.771	-0.219 Per upper limit normal Interval -4.625 to 3.625	—
Median Change From Baseline in Serum ALT Over Time Week 16	0.021 Per upper limit normal Interval -1.417 to 2.583	-0.125 Per upper limit normal Interval -1.292 to 1.104	-0.208 Per upper limit normal Interval -4.0 to 0.917	—
Median Change From Baseline in Serum ALT Over Time Week 22	0.010 Per upper limit normal Interval -1.313 to 2.021	-0.146 Per upper limit normal Interval -1.521 to 1.813	-0.198 Per upper limit normal Interval -5.979 to 1.354	—
Median Change From Baseline in Serum ALT Over Time Week 28	-0.021 Per upper limit normal Interval -2.104 to 3.854	-0.146 Per upper limit normal Interval -1.938 to 2.521	-0.208 Per upper limit normal Interval -5.771 to 2.563	—
Median Change From Baseline in Serum ALT Over Time Week 34	-0.042 Per upper limit normal Interval -1.313 to 2.979	-0.188 Per upper limit normal Interval -1.854 to 1.583	-0.271 Per upper limit normal Interval -6.188 to 4.042	—
Median Change From Baseline in Serum ALT Over Time Week 40	-0.021 Per upper limit normal Interval -1.771 to 4.625	-0.104 Per upper limit normal Interval -2.292 to 1.625	-0.208 Per upper limit normal Interval -3.792 to 2.0	—
Median Change From Baseline in Serum ALT Over Time Week 46	-0.063 Per upper limit normal Interval -1.771 to 7.938	-0.146 Per upper limit normal Interval -2.104 to 2.146	-0.229 Per upper limit normal Interval -2.833 to 1.625	—
Median Change From Baseline in Serum ALT Over Time Week 52	0.021 Per upper limit normal Interval -1.917 to 3.542	-0.083 Per upper limit normal Interval -1.396 to 2.021	-0.271 Per upper limit normal Interval -4.125 to 4.042	—
Median Change From Baseline in Serum ALT Over Time Post-treatment	-0.042 Per upper limit normal Interval -2.917 to 6.458	-0.146 Per upper limit normal Interval -2.75 to 1.667	-0.229 Per upper limit normal Interval -3.75 to 4.313	—

SECONDARY outcome

Timeframe: Baseline and Week 52

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants 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.	GI262570 0.5mg n=78 Participants 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.	GI262570 1.0mg n=82 Participants 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.	GI262570 1.0 mg Once Daily 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.
Mean Change From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 52	-0.020 Log10 International unit per milliliter Standard Deviation 0.4264	-0.006 Log10 International unit per milliliter Standard Deviation 0.3760	0.040 Log10 International unit per milliliter Standard Deviation 0.4803	—

SECONDARY outcome

Timeframe: Baseline and up to 4 weeks post-treatment (52 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants 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.	GI262570 0.5mg n=89 Participants 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.	GI262570 1.0mg n=88 Participants 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.	GI262570 1.0 mg Once Daily 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.
Median Change From Baseline in Serum HCV RNA Levels Over Time Week 28	0.112 Log10 International unit per milliliter Interval -1.02 to 0.82	0.011 Log10 International unit per milliliter Interval -0.93 to 1.61	0.071 Log10 International unit per milliliter Interval -0.62 to 2.41	—
Median Change From Baseline in Serum HCV RNA Levels Over Time Week 52	-0.059 Log10 International unit per milliliter Interval -0.94 to 1.54	0.034 Log10 International unit per milliliter Interval -0.9 to 1.47	0.013 Log10 International unit per milliliter Interval -0.82 to 2.48	—
Median Change From Baseline in Serum HCV RNA Levels Over Time Post-treatment	0.024 Log10 International unit per milliliter Interval -0.93 to 1.41	0.039 Log10 International unit per milliliter Interval -0.84 to 1.18	0.026 Log10 International unit per milliliter Interval -2.56 to 1.86	—

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GI262570 0.5mg n=19 Participants 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.	GI262570 1.0mg n=8 Participants 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.	GI262570 1.0 mg Once Daily n=14 Participants 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.
Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length 'Tau' (AUC [0-tau]) of GI262570 on Week 2	68.65 Hour nanograms per milliliter Geometric Coefficient of Variation 64	88.87 Hour nanograms per milliliter Geometric Coefficient of Variation 34	151.11 Hour nanograms per milliliter Geometric Coefficient of Variation 55	141.03 Hour nanograms per milliliter Geometric Coefficient of Variation 29

SECONDARY outcome

Timeframe: 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