Sofosbuvir in Combination With Pegylated Interferon and Ribavirin and in Treatment-Naive Hepatitis C-infected Patients

A Multi-center, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Pegylated Interferon and Ribavirin in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1, and an Open Label Assessment of PSI-7977 in Patients With HCV Genotypes 2 or 3

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01188772

Enrollment

147

Registered

2010-08-25

Start date

2010-08-31

Completion date

2012-05-31

Last updated

2014-04-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C Virus

Keywords

Hepatitis C Virus, HCV, hepatitis, Genotype 1, Genotype 2, Genotype 3

Brief summary

Genotype 1: Participants with genotype 1 hepatitis C (HCV) infection were randomized to receive sofosbuvir (GS-7977; PSI-7977) 200 mg or 400 mg, or matching placebo, plus pegylated interferon alfa 2a (PEG) and ribavirin (RBV) for 12 weeks, followed by PEG+RBV for an up to an additional 36 weeks. Randomization was stratified by IL28B status (CC, CT, TT) and HCV RNA level (\< 800,000 IU/ml or ≥ 800,000 IU/ml) at baseline. Participants were randomized in a 2:2:1 manner; those who achieved an extended rapid virologic response (eRVR) (HCV RNA \< lower limit of detection \[15 IU/mL\] from Weeks 4 through 12) received an additional 12 weeks of PEG+RBV. Subjects not achieving eRVR received an additional 36 weeks of PEG+RBV. Genotype 2 and 3: Participants with genotype 2 or 3 hepatitis C (HCV) received sofosbuvir 400 mg plus PEG+RBV for 12 weeks.

Interventions

DRUGSofosbuvir

Sofosbuvir tablets were administered orally once daily.

DRUGPlacebo to match sofosbuvir

Placebo tablets to match sofosbuvir were administered orally once daily.

DRUGPEG

Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.

DRUGRBV

Ribavirin (RBV) was administered as a tablet orally according to package insert dosing recommendations (Genotype 1: \< 75kg = 1000 mg and ≥ 75 kg = 1200 mg; Genotype 2/3: 800 mg).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Males or females aged 18 to 70 years, inclusive, at screening * Documented chronic genotype 1, 2, or 3 HCV infection * No previous treatment with HCV antiviral mediations * Body mass index (BMI) of greater than 18 kg/m2, but not exceeding 36 kg/m2. * Liver biopsy obtained within 3 years prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic as judged by a local pathologist * Willing to refrain from beginning any new exercise regimens during the first 3 months of the study * Fasting blood glucose ≤ 300 mg/dl and/or glycosylated hemoglobin (HbA1c) ≤ 8 * History of hypertension only if managed effectively on a stable regimen of two or fewer antihypertensives for at least three (3) months prior to screening

Exclusion criteria

* Females who were breastfeeding * Males and females of reproductive potential who are unwilling to use an effective, protocol-specified method(s) of contraception during the study * Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab. * History of any other clinically significant chronic liver disease * Treatment with herbal/natural remedies with antiviral activity within 30 days prior to baseline. * Significant history of immunologically mediated disease, cardiac or pulmonary disease, seizure disorder or anticonvulsant use * History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease * Use of medications associated with QT prolongation within 30 days prior to dosing * Screening electrocardiogram (ECG) QTc value greater than 450 ms and/or clinically significant ECG findings * Personal or family history of Torsade de pointes. * Positive results for drugs of abuse test at screening * Abnormal hematological and biochemical parameters, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5 times the upper limit of the normal range (ULN) * History of major organ transplantation with an existing functional graft * History of uncontrolled thyroid disease or abnormal thyroid-stimulating hormone (TSH) levels at screening * Clinically significant drug allergy to nucleoside/nucleotide analogs * History or current evidence of psychiatric illness, immunologic disorder, pulmonary, cardiac disease, seizure disorder, cancer or history of malignancy that in the opinion of the investigator makes the patient unsuitable for the study * History of systemic antineoplastic or immunomodulatory treatment within 6 months prior to dosing, or the expectation of such treatment during the study

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Baseline to Week 12 plus 30 days	Adverse events (AEs) occurring during the sofosbuvir treatment period and for 30 days following the last dose of sofosbuvir were summarized across the participant population. A participant was counted once if they had a qualifying event.

Secondary

Measure	Time frame	Description
Percentage of Participants With Rapid Virologic Response at Week 4	Week 4	Rapid virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 4 (Day 29)
Percentage of Participants With Complete Early Virologic Response at Week 12	Week 12	Complete early virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 12
Percentage of Participants With Extended Rapid Virologic Response	Week 4 to Week 12	Extended rapid virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 4 (Day 29) which was maintained through Week 12.
Percentage of Participants With Virologic Response at the End of Treatment	Week 48 (genotype 1) or Week 12 (genotype 2/3)	End-of-treatment virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at the last on-treatment visit.
Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	Post-treatment Weeks 12 and 24	SVR12 and SVR24 were defined as HCV RNA below the limit of detection (\< 15 IU/mL) at post-treatment Weeks 12 and 24, respectively.
Plasma Pharmacokinetics of GS-331007 (Cmax at Day 8)	1, 2, 4, 8, and 12 hours postdose	The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the maximum observed concentration of drug in plasma (Cmax) at Day 8. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.
Change in HCV RNA From Baseline to Week 12	Baseline to Week 12	—
Plasma Pharmacokinetics of GS-331007 (Cmax at Day 29)	1, 2, 4, 8, and 12 hours postdose	The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the Cmax at Day 29. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.
Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 8)	1, 2, 4, 8, and 12 hours postdose	The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) at Day 8. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.
Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 15)	1, 2, 4, 8, and 12 hours postdose	The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) at Day 15. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.
Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 29)	1, 2, 4, 8, and 12 hours postdose	The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) at Day 29. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.
Percentage of Participants Who Developed Resistance to Sofosbuvir	Baseline to Week 12	Resistance monitoring was completed in all subjects who received sofosbuvir and who had non-response, viral rebound, virologic breakthrough, or HCV RNA plateaus between Day 0 and Week 24.
Plasma Pharmacokinetics of GS-331007 (Cmax at Day 15)	1, 2, 4, 8, and 12 hours postdose	The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the Cmax at Day 15. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.

Countries

Puerto Rico, United States

Participant flow

Recruitment details

Subjects were enrolled in a total of 22 study sites in the United States. The first participant was screened on 16 August 2010. The last participant observation was on 11 May 2012.

Pre-assignment details

147 participants were randomized, and 146 participants received at least one dose of study drug, and comprise the Safety Analysis Set.

Participants by arm

Arm	Count
Sofosbuvir 200 mg (Genotype 1) Sofosbuvir 200 mg+PEG+RBV for 12 weeks; PEG+RBV for up to an additional 36 weeks	48
Sofosbuvir 400 mg (Genotype 1) Sofosbuvir 400 mg+PEG+RBV for 12 weeks; PEG+RBV for up to an additional 36 weeks	47
Placebo (Genotype 1) Placebo to match sofosbuvir+PEG+RBV for 12 weeks; PEG+RBV for up to an additional 36 weeks	26
Sofosbuvir 400 mg (Genotype 2/3) Sofosbuvir 400 mg+PEG+RBV for 12 weeks	25
Total	146

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	1	2	0
Overall Study	Lost to Follow-up	4	1	1	1
Overall Study	Non-responder	0	0	3	0
Overall Study	Physician Decision	0	0	1	0
Overall Study	Randomized but Not Treated	0	1	0	0
Overall Study	Terminated by Sponsor	0	0	1	0
Overall Study	Treatment Failure	0	0	1	0
Overall Study	Virologic Failure	1	0	0	0
Overall Study	Withdrawal by Subject	0	0	2	0

Baseline characteristics

Characteristic	Sofosbuvir 200 mg (Genotype 1)	Total	Sofosbuvir 400 mg (Genotype 2/3)	Placebo (Genotype 1)	Sofosbuvir 400 mg (Genotype 1)
Age, Continuous	48.4 years STANDARD_DEVIATION 11.49	49.2 years STANDARD_DEVIATION 10.41	47.2 years STANDARD_DEVIATION 11.07	48.6 years STANDARD_DEVIATION 9.35	51.4 years STANDARD_DEVIATION 9.37
Alanine Aminotransferase (ALT)	81.9 IU/L STANDARD_DEVIATION 66.07	78.7 IU/L STANDARD_DEVIATION 61.53	74.5 IU/L STANDARD_DEVIATION 54.81	81.4 IU/L STANDARD_DEVIATION 49.14	76.1 IU/L STANDARD_DEVIATION 67.56
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	20 Participants	8 Participants	1 Participants	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants	125 Participants	17 Participants	24 Participants	41 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Hepatitis C (HCV) RNA	6.54 log10 IU/mL STANDARD_DEVIATION 0.63	6.40 log10 IU/mL STANDARD_DEVIATION 0.76	6.07 log10 IU/mL STANDARD_DEVIATION 0.794	6.50 log10 IU/mL STANDARD_DEVIATION 0.762	6.39 log10 IU/mL STANDARD_DEVIATION 0.827
IL28b Genotype CC	21 participants	57 participants	7 participants	11 participants	18 participants
IL28b Genotype CT	24 participants	71 participants	17 participants	11 participants	19 participants
IL28b Genotype TT	3 participants	18 participants	1 participants	4 participants	10 participants
Liver Biopsy Fibrosis Score Bridging Fibrosis	1 participants	5 participants	0 participants	2 participants	2 participants
Liver Biopsy Fibrosis Score Cirrhosis	0 participants	0 participants	0 participants	0 participants	0 participants
Liver Biopsy Fibrosis Score None or Minimal Fibrosis	12 participants	29 participants	7 participants	3 participants	7 participants
Liver Biopsy Fibrosis Score Portal Fibrosis	35 participants	112 participants	18 participants	21 participants	38 participants
Race/Ethnicity, Customized American Indian or Alaska native	0 participants	1 participants	0 participants	0 participants	1 participants
Race/Ethnicity, Customized Asian	1 participants	1 participants	0 participants	0 participants	0 participants
Race/Ethnicity, Customized Black or African American	6 participants	22 participants	4 participants	5 participants	7 participants
Race/Ethnicity, Customized Other	2 participants	5 participants	1 participants	0 participants	2 participants
Race/Ethnicity, Customized White	39 participants	117 participants	20 participants	21 participants	37 participants
Sex: Female, Male Female	15 Participants	57 Participants	9 Participants	7 Participants	26 Participants
Sex: Female, Male Male	33 Participants	89 Participants	16 Participants	19 Participants	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	47 / 48	46 / 47	26 / 26	24 / 25
serious Total, serious adverse events	1 / 48	3 / 47	1 / 26	0 / 25

Outcome results

Primary

Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period

Adverse events (AEs) occurring during the sofosbuvir treatment period and for 30 days following the last dose of sofosbuvir were summarized across the participant population. A participant was counted once if they had a qualifying event.

Time frame: Baseline to Week 12 plus 30 days

Population: Safety Analysis Set: participants were randomized and received at least one dose of study drug

Arm	Measure	Group	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	AE leading to drug discontinuation	4.2 percentage of participants
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Drug-related AE	97.9 percentage of participants
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Serious AE	2.1 percentage of participants
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Grade 3 or higher AE	10.4 percentage of participants
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Any AE	97.9 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Grade 3 or higher AE	21.3 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	AE leading to drug discontinuation	6.4 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Serious AE	6.4 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Drug-related AE	95.7 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Any AE	97.9 percentage of participants
Placebo (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Grade 3 or higher AE	11.5 percentage of participants
Placebo (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Any AE	100.0 percentage of participants
Placebo (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Drug-related AE	100.0 percentage of participants
Placebo (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	AE leading to drug discontinuation	11.5 percentage of participants
Placebo (Genotype 1)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Serious AE	3.8 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	AE leading to drug discontinuation	0.0 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Drug-related AE	96.0 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Any AE	96.0 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Grade 3 or higher AE	12.0 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Serious AE	0.0 percentage of participants

Secondary

Change in HCV RNA From Baseline to Week 12

Time frame: Baseline to Week 12

Population: Participants in the Safety Analysis Set with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
Sofosbuvir 200 mg (Genotype 1)	Change in HCV RNA From Baseline to Week 12	-5.39 log10 IU/mL	Standard Deviation 0.63
Sofosbuvir 400 mg (Genotype 1)	Change in HCV RNA From Baseline to Week 12	-5.20 log10 IU/mL	Standard Deviation 0.842
Placebo (Genotype 1)	Change in HCV RNA From Baseline to Week 12	-4.16 log10 IU/mL	Standard Deviation 1.728
Sofosbuvir 400 mg (Genotype 2/3)	Change in HCV RNA From Baseline to Week 12	-4.95 log10 IU/mL	Standard Deviation 0.803

Secondary

Percentage of Participants Who Developed Resistance to Sofosbuvir

Resistance monitoring was completed in all subjects who received sofosbuvir and who had non-response, viral rebound, virologic breakthrough, or HCV RNA plateaus between Day 0 and Week 24.

Time frame: Baseline to Week 12

Population: Participants in the Safety Analysis Set who received a regimen containing sofosbuvir were analyzed.

Arm	Measure	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants Who Developed Resistance to Sofosbuvir	0.0 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants Who Developed Resistance to Sofosbuvir	0.0 percentage of participants
Placebo (Genotype 1)	Percentage of Participants Who Developed Resistance to Sofosbuvir	0.0 percentage of participants

Secondary

Percentage of Participants With Complete Early Virologic Response at Week 12

Complete early virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 12

Time frame: Week 12

Population: Safety Analysis Set

Arm	Measure	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants With Complete Early Virologic Response at Week 12	100.0 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants With Complete Early Virologic Response at Week 12	91.5 percentage of participants
Placebo (Genotype 1)	Percentage of Participants With Complete Early Virologic Response at Week 12	61.5 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants With Complete Early Virologic Response at Week 12	96.0 percentage of participants

Secondary

Percentage of Participants With Extended Rapid Virologic Response

Extended rapid virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 4 (Day 29) which was maintained through Week 12.

Time frame: Week 4 to Week 12

Population: Safety Analysis Set

Arm	Measure	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants With Extended Rapid Virologic Response	97.9 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants With Extended Rapid Virologic Response	91.5 percentage of participants
Placebo (Genotype 1)	Percentage of Participants With Extended Rapid Virologic Response	19.2 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants With Extended Rapid Virologic Response	96.0 percentage of participants

Secondary

Percentage of Participants With Rapid Virologic Response at Week 4

Rapid virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 4 (Day 29)

Time frame: Week 4

Population: Safety Analysis Set

Arm	Measure	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants With Rapid Virologic Response at Week 4	97.9 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants With Rapid Virologic Response at Week 4	97.9 percentage of participants
Placebo (Genotype 1)	Percentage of Participants With Rapid Virologic Response at Week 4	19.2 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants With Rapid Virologic Response at Week 4	96.0 percentage of participants

Secondary

Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)

SVR12 and SVR24 were defined as HCV RNA below the limit of detection (\< 15 IU/mL) at post-treatment Weeks 12 and 24, respectively.

Time frame: Post-treatment Weeks 12 and 24

Population: Safety Analysis Set

Arm	Measure	Group	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR12	89.6 percentage of participants
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR24	89.6 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR24	91.5 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR12	91.5 percentage of participants
Placebo (Genotype 1)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR12	57.7 percentage of participants
Placebo (Genotype 1)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR24	57.7 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR12	92.0 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)	SVR24	92.0 percentage of participants

Secondary

Percentage of Participants With Virologic Response at the End of Treatment

End-of-treatment virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at the last on-treatment visit.

Time frame: Week 48 (genotype 1) or Week 12 (genotype 2/3)

Population: Participants in the Safety Analysis Set with available data were analyzed. One participant in the Sofosbuvir 400 mg (Genotype 2/3) Group was lost to follow up before the end of treatment and is not included in this analysis.

Arm	Measure	Value (NUMBER)
Sofosbuvir 200 mg (Genotype 1)	Percentage of Participants With Virologic Response at the End of Treatment	93.8 percentage of participants
Sofosbuvir 400 mg (Genotype 1)	Percentage of Participants With Virologic Response at the End of Treatment	100.0 percentage of participants
Placebo (Genotype 1)	Percentage of Participants With Virologic Response at the End of Treatment	61.5 percentage of participants
Sofosbuvir 400 mg (Genotype 2/3)	Percentage of Participants With Virologic Response at the End of Treatment	100.0 percentage of participants

Secondary

Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 15)

The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) at Day 15. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.