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Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency

A Phase 2b, Open-Label Study of 200 mg or 400 mg Sofosbuvir+RBV for 24 Weeks in Genotype 1 or 3 and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) Tablet for 12 Weeks in Genotype 1 or 4 HCV Infected Subjects With Renal Insufficiency

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01958281
Enrollment
38
Registered
2013-10-09
Start date
2013-10-07
Completion date
2017-10-19
Last updated
2018-08-08

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

Conditions

HCV Infection

Brief summary

The primary objectives of this study are to evaluate the safety and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) for 24 weeks and ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks, and to evaluate the steady state pharmacokinetics (PK) of SOF and its metabolites and LDV in participants with genotype (GT) 1, 3, or 4 hepatitis C virus (HCV) infection who have chronic renal insufficiency (impaired kidney function).

Interventions

DRUGSOF

Tablet(s) administered orally once daily

DRUGRBV

200 mg tablet administered orally once daily

DRUGLDV/SOF

90/400 mg fixed-dose combination (FDC) tablet administered orally once daily

Sponsors

Gilead Sciences
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

Key Inclusion Criteria: * Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection * Cohort 3: chronic genotype 1 or 4 HCV infection * HCV RNA ≥ 10\^4 IU/mL at screening * Screening labs within defined thresholds * Cirrhosis determination at screening Key

Exclusion criteria

* Females who are pregnant or nursing or males who have a pregnant partner * Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3) * Current of prior history of hepatic decompensation * Infection with hepatitis B virus (HBV) or HIV * History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol Note: Other protocol defined Inclusion/

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)Posttreatment Week 12SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Experiencing Treatment-Emergent Adverse EventsUp to 24 weeks plus 30 days—
Percentage of Participants Experiencing Treatment-Emergent Laboratory AbnormalitiesUp to 24 weeks plus 30 daysTreatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any time postbaseline up to the date of last dose of study drug plus 30 days.
Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) AbnormalitiesUp to 24 weeks plus 30 days—
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign AbnormalitiesUp to 24 weeks plus 30 days—
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2Cmax is defined as the maximum concentration of drug.
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12Cmax is defined as the maximum concentration of drug.
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4Cmax is defined as the maximum concentration of drug.
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4Ctau is defined as the observed drug concentration at the end of the dosing interval.

Secondary

MeasureTime frameDescription
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4Tlast is defined as the time (observed time point) of Clast.
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)Posttreatment Week 4SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)Posttreatment Week 24SVR4 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.
Percentage of Participants With Overall Virologic FailureUp to Posttreatment Week 24Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2Clast is defined as the last observable concentration of drug.
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12Clast is defined as the last observable concentration of drug.
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4Clast is defined as the last observable concentration of drug.
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2Tlast is defined as the time (observed time point) of Clast.
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12Tlast is defined as the time (observed time point) of Clast.

Countries

New Zealand, Puerto Rico, United States

Participant flow

Recruitment details

Participants were enrolled at study sites in the United States and New Zealand. The first participant was screened on 07 October 2013. The last study visit occurred on 19 October 2017.

Pre-assignment details

32 participants were screened for Cohorts 1 and 2 and 33 participants were screened for Cohort 3.

Participants by arm

ArmCount
SOF 200 mg + RBV 200 mg (Cohort 1)
SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks
10
SOF 400 mg + RBV 200 mg (Cohort 2)
SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks
10
LDV/SOF (Cohort 3)
LDV/SOF 90/400 mg FDC tablet for 12 weeks
18
Total38

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyAdverse Event020
Overall StudyLack of Efficacy520
Overall StudyWithdrew Consent100

Baseline characteristics

CharacteristicSOF 200 mg + RBV 200 mg (Cohort 1)TotalLDV/SOF (Cohort 3)SOF 400 mg + RBV 200 mg (Cohort 2)
Age, Continuous62 years
STANDARD_DEVIATION 6.5
58.9 years
STANDARD_DEVIATION 7.76
57 years
STANDARD_DEVIATION 7.5
58 years
STANDARD_DEVIATION 9
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants7 Participants4 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
8 Participants31 Participants14 Participants9 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
HCV genotype
Genotype 1a
7 Participants27 Participants14 Participants6 Participants
HCV genotype
Genotype 1b
2 Participants8 Participants4 Participants2 Participants
HCV genotype
Genotype 3a
1 Participants3 Participants0 Participants2 Participants
IL28b Status
CC
2 Participants8 Participants1 Participants5 Participants
IL28b Status
CT
6 Participants21 Participants11 Participants4 Participants
IL28b Status
TT
2 Participants9 Participants6 Participants1 Participants
Race/Ethnicity, Customized
Asian
1 Participants1 Participants0 Participants0 Participants
Race/Ethnicity, Customized
Black or African American
5 Participants19 Participants10 Participants4 Participants
Race/Ethnicity, Customized
Hawaiian or Pacific Islander
0 Participants1 Participants0 Participants1 Participants
Race/Ethnicity, Customized
Other
2 Participants2 Participants0 Participants0 Participants
Race/Ethnicity, Customized
White
2 Participants15 Participants8 Participants5 Participants
Region of Enrollment
New Zealand
7 Participants14 Participants1 Participants6 Participants
Region of Enrollment
United States
3 Participants24 Participants17 Participants4 Participants
Sex: Female, Male
Female
4 Participants18 Participants12 Participants2 Participants
Sex: Female, Male
Male
6 Participants20 Participants6 Participants8 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 100 / 100 / 18
other
Total, other adverse events
10 / 109 / 1012 / 18
serious
Total, serious adverse events
2 / 102 / 104 / 18

Outcome results

Primary

Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities

Time frame: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities5.6 percentage of participants
Primary

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Time frame: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants Experiencing Treatment-Emergent Adverse Events100.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants Experiencing Treatment-Emergent Adverse Events90.0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants Experiencing Treatment-Emergent Adverse Events72.2 percentage of participants
Primary

Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities

Time frame: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities10.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities0 percentage of participants
Primary

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

Treatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any time postbaseline up to the date of last dose of study drug plus 30 days.

Time frame: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities100.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities100.0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities100.0 percentage of participants
Primary

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Time frame: Posttreatment Week 12

Population: Full Analysis Set: participants who were enrolled and took at least 1 dose of study drug.

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)40.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)60.0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)100.0 percentage of participants
Primary

Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set (all enrolled participants who took at least 1 dose of study drug and have at least 1 nonmissing postdose PK concentration value) from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1093.9 h*ng/mLStandard Deviation 703.03
SOF 200 mg + RBV 200 mg (Cohort 1)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665002120.2 h*ng/mLStandard Deviation 837.51
SOF 200 mg + RBV 200 mg (Cohort 1)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100731859.4 h*ng/mLStandard Deviation 12621.62
SOF 200 mg + RBV 200 mg (Cohort 1)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV22253.9 h*ng/mLStandard Deviation 6860.72
SOF 400 mg + RBV 200 mg (Cohort 2)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV23595.5 h*ng/mLStandard Deviation 9636.77
SOF 400 mg + RBV 200 mg (Cohort 2)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1630.5 h*ng/mLStandard Deviation 851.33
SOF 400 mg + RBV 200 mg (Cohort 2)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100751989.6 h*ng/mLStandard Deviation 29461.91
SOF 400 mg + RBV 200 mg (Cohort 2)Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665004026.2 h*ng/mLStandard Deviation 1848.5
Primary

PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF3536.8 h*ng/mLStandard Deviation 2040.59
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-5665007716.6 h*ng/mLStandard Deviation 3534.76
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-33100771463.3 h*ng/mLStandard Deviation 28979.92
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV18460.1 h*ng/mLStandard Deviation 19999.95
Primary

PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1302.7 h*ng/mLStandard Deviation 652.18
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665002223.2 h*ng/mLStandard Deviation 877.2
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100731078.3 h*ng/mLStandard Deviation 16745.94
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV45341.9 h*ng/mLStandard Deviation 8712.71
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV50471.2 h*ng/mLStandard Deviation 23077.43
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1571.3 h*ng/mLStandard Deviation 944.71
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100746810.1 h*ng/mLStandard Deviation 25249.07
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665003213.9 h*ng/mLStandard Deviation 1221.71
Primary

PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Cmax is defined as the maximum concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF2018.1 ng/mLStandard Deviation 1110.56
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-5665001021.6 ng/mLStandard Deviation 359.13
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-3310073570.0 ng/mLStandard Deviation 1325.31
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV903.4 ng/mLStandard Deviation 844.7
Primary

PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Cmax is defined as the maximum concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF903.9 ng/mLStandard Deviation 598.55
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-566500352.2 ng/mLStandard Deviation 127.83
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310071727.0 ng/mLStandard Deviation 775.37
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV2458.8 ng/mLStandard Deviation 437.54
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV2589.4 ng/mLStandard Deviation 1159.66
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1422.9 ng/mLStandard Deviation 1390.47
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310072645.0 ng/mLStandard Deviation 1482.1
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-566500509.1 ng/mLStandard Deviation 216.71
Primary

PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Cmax is defined as the maximum concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF575.9 ng/mLStandard Deviation 487.66
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-566500308.3 ng/mLStandard Deviation 132.6
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310071750.0 ng/mLStandard Deviation 578.56
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV1373.1 ng/mLStandard Deviation 496.37
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV1373.8 ng/mLStandard Deviation 550.23
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF976.8 ng/mLStandard Deviation 712.04
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310072721.4 ng/mLStandard Deviation 1452.86
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-566500538.3 ng/mLStandard Deviation 241.51
Primary

PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF2.9 ng/mLStandard Deviation 1.57
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-56650059.3 ng/mLStandard Deviation 88.08
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-3310072568.2 ng/mLStandard Deviation 1106.81
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV705.0 ng/mLStandard Deviation 876.54
Primary

PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOFNA ng/mL—
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665002.3 ng/mLStandard Deviation 7.12
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-331007952.5 ng/mLStandard Deviation 586.51
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV1567.5 ng/mLStandard Deviation 529.35
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV1968.6 ng/mLStandard Deviation 884.99
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOFNA ng/mL—
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310071356.0 ng/mLStandard Deviation 681.23
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-56650010.4 ng/mLStandard Deviation 11.07
Primary

PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOFNA ng/mL—
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665003.7 ng/mLStandard Deviation 7.88
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310071023.0 ng/mLStandard Deviation 477.15
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV759.1 ng/mLStandard Deviation 240.04
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV818.8 ng/mLStandard Deviation 323.67
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOFNA ng/mL—
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310071736.1 ng/mLStandard Deviation 1110.41
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-56650020.8 ng/mLStandard Deviation 20.51
Secondary

Percentage of Participants With Overall Virologic Failure

Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.

Time frame: Up to Posttreatment Week 24

Population: Full Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants With Overall Virologic Failure50.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants With Overall Virologic Failure40.0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants With Overall Virologic Failure0 percentage of participants
Secondary

Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)

SVR4 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.

Time frame: Posttreatment Week 24

Population: Full Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)40.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)60.0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)100.0 percentage of participants
Secondary

Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)

SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.

Time frame: Posttreatment Week 4

Population: Full Analysis Set

ArmMeasureValue (NUMBER)
SOF 200 mg + RBV 200 mg (Cohort 1)Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)40.0 percentage of participants
SOF 400 mg + RBV 200 mg (Cohort 2)Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)60.0 percentage of participants
LDV/SOF (Cohort 3)Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)100.0 percentage of participants
Secondary

PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF3519.3 h*ng/mLStandard Deviation 2045.64
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-5665007657.6 h*ng/mLStandard Deviation 3555.57
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-33100769177.7 h*ng/mLStandard Deviation 31267.56
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV18044.3 h*ng/mLStandard Deviation 20210.19
Secondary

PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1177.7 h*ng/mLStandard Deviation 674.86
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665001867.1 h*ng/mLStandard Deviation 839.39
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100731078.3 h*ng/mLStandard Deviation 16745.94
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV45341.9 h*ng/mLStandard Deviation 8712.71
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV50471.2 h*ng/mLStandard Deviation 23077.43
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1548.1 h*ng/mLStandard Deviation 955.12
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100746810.1 h*ng/mLStandard Deviation 25249.07
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665003133.0 h*ng/mLStandard Deviation 1230.39
Secondary

PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF885.0 h*ng/mLStandard Deviation 710.72
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665001973.3 h*ng/mLStandard Deviation 851.52
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100731859.4 h*ng/mLStandard Deviation 12621.62
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV22253.9 h*ng/mLStandard Deviation 6860.72
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV23595.5 h*ng/mLStandard Deviation 9636.77
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1607.7 h*ng/mLStandard Deviation 854.7
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100751989.6 h*ng/mLStandard Deviation 29461.91
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665003965.7 h*ng/mLStandard Deviation 1900.25
Secondary

PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Clast is defined as the last observable concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF56.3 ng/mLStandard Deviation 216.91
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-56650070.5 ng/mLStandard Deviation 97.14
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-3310072570.6 ng/mLStandard Deviation 1071.71
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV700.6 ng/mLStandard Deviation 848.9
Secondary

PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Clast is defined as the last observable concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF100.7 ng/mLStandard Deviation 158.83
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-56650072.2 ng/mLStandard Deviation 80.16
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-331007952.5 ng/mLStandard Deviation 586.51
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV1741.3 ng/mLStandard Deviation 417.42
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV2040.9 ng/mLStandard Deviation 917.23
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF22.7 ng/mLStandard Deviation 30.15
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310071412.9 ng/mLStandard Deviation 705.06
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-56650032.1 ng/mLStandard Deviation 22.04
Secondary

PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Clast is defined as the last observable concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF68.0 ng/mLStandard Deviation 100.22
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-56650037.6 ng/mLStandard Deviation 18.84
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310071023.0 ng/mLStandard Deviation 477.15
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV759.1 ng/mLStandard Deviation 240.04
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV818.8 ng/mLStandard Deviation 323.67
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF21.3 ng/mLStandard Deviation 22.22
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310071736.1 ng/mLStandard Deviation 1110.41
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-56650035.8 ng/mLStandard Deviation 21.06
Secondary

PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF1.18 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-5665004.02 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-33100739.30 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV25.96 hours
Secondary

PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665003.03 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF0.48 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100722.03 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV61.25 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV91.62 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100733.54 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF0.57 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665003.88 hours
Secondary

PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF0.67 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665003.31 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100730.53 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV46.89 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV56.43 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF0.67 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100729.05 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665003.88 hours
Secondary

PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Tlast is defined as the time (observed time point) of Clast.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF12.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-56650024.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-33100724.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV24.00 hours
Secondary

PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Tlast is defined as the time (observed time point) of Clast.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF4.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-56650012.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100724.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV24.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV24.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF4.03 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-33100724.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-56650024.00 hours
Secondary

PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Tlast is defined as the time (observed time point) of Clast.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF4.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-56650012.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100724.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV24.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV24.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF6.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-33100724.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-56650024.00 hours
Secondary

PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF1.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-5665002.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-3310074.02 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV6.00 hours
Secondary

PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1.04 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665002.17 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310075.11 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV2.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV1.50 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF0.50 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310075.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665002.00 hours
Secondary

PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEDIAN)
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665002.17 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310074.00 hours
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV2.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV2.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1.50 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310076.00 hours
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665004.00 hours
Secondary

PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Population: Participants in the PK Analysis Set from Cohort 3 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)SOF0.6033 1/hourStandard Deviation 0.24057
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-5665000.1705 1/hourStandard Deviation 0.04602
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)GS-3310070.0214 1/hourStandard Deviation 0.01222
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)LDV0.0305 1/hourStandard Deviation 0.01226
Secondary

PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 with available data were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1.4002 1/hourStandard Deviation 0.29086
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665000.2232 1/hourStandard Deviation 0.05244
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310070.0332 1/hourStandard Deviation 0.01388
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV0.0124 1/hourStandard Deviation 0.0058
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)RBV0.0085 1/hourStandard Deviation 0.00509
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)SOF1.2154 1/hourStandard Deviation 0.241
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-3310070.0313 1/hourStandard Deviation 0.021
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)GS-5665000.1818 1/hourStandard Deviation 0.06121
Secondary

PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

Population: Participants in the PK Analysis Set from Cohorts 1 and 2 were analyzed.

ArmMeasureGroupValue (MEAN)Dispersion
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1.0419 1/hourStandard Deviation 0.28621
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665000.2078 1/hourStandard Deviation 0.04748
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310070.0275 1/hourStandard Deviation 0.01331
SOF 200 mg + RBV 200 mg (Cohort 1)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV0.0165 1/hourStandard Deviation 0.00524
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)RBV0.0141 1/hourStandard Deviation 0.00658
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)SOF1.0155 1/hourStandard Deviation 0.33118
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-3310070.0273 1/hourStandard Deviation 0.01711
SOF 400 mg + RBV 200 mg (Cohort 2)PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)GS-5665000.1771 1/hourStandard Deviation 0.05802

Source: ClinicalTrials.gov · Data processed: Feb 27, 2026