Trial Outcomes & Findings for Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency (NCT NCT01958281)

NCT ID: NCT01958281

Last Updated: 2018-08-08

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

Posttreatment Week 12

Results posted on

2018-08-08

Participant Flow

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.

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

Participant milestones

Participant milestones
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) Sofosbuvir (SOF) 200 mg tablet once daily + ribavirin (RBV) 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet for 12 weeks
Overall Study STARTED	10	10	18
Overall Study COMPLETED	4	6	18
Overall Study NOT COMPLETED	6	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) Sofosbuvir (SOF) 200 mg tablet once daily + ribavirin (RBV) 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks
Overall Study Lack of Efficacy	5	2
Overall Study Adverse Event	0	2
Overall Study Withdrew Consent	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks	Total n=38 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 6.5 • n=5 Participants	58 years STANDARD_DEVIATION 9.0 • n=7 Participants	57 years STANDARD_DEVIATION 7.5 • n=5 Participants	58.9 years STANDARD_DEVIATION 7.76 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	12 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (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
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	19 Participants n=4 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Hawaiian or Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment New Zealand	7 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	14 Participants n=4 Participants
Region of Enrollment United States	3 Participants n=5 Participants	4 Participants n=7 Participants	17 Participants n=5 Participants	24 Participants n=4 Participants
HCV genotype Genotype 1a	7 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants	27 Participants n=4 Participants
HCV genotype Genotype 1b	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
HCV genotype Genotype 3a	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
IL28b Status CC	2 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
IL28b Status CT	6 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants	21 Participants n=4 Participants
IL28b Status TT	2 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Posttreatment Week 12

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

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	40.0 percentage of participants Interval 12.2 to 73.8	60.0 percentage of participants Interval 26.2 to 87.8	100.0 percentage of participants Interval 81.5 to 100.0

PRIMARY outcome

Timeframe: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants Experiencing Treatment-Emergent Adverse Events	100.0 percentage of participants	90.0 percentage of participants	72.2 percentage of participants

PRIMARY outcome

Timeframe: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants

PRIMARY outcome

Timeframe: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities	0 percentage of participants	0 percentage of participants	5.6 percentage of participants

PRIMARY outcome

Timeframe: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities	10.0 percentage of participants	0 percentage of participants	0 percentage of participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	1093.9 h*ng/mL Standard Deviation 703.03	1630.5 h*ng/mL Standard Deviation 851.33	—
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	2120.2 h*ng/mL Standard Deviation 837.51	4026.2 h*ng/mL Standard Deviation 1848.50	—
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	31859.4 h*ng/mL Standard Deviation 12621.62	51989.6 h*ng/mL Standard Deviation 29461.91	—
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	22253.9 h*ng/mL Standard Deviation 6860.72	23595.5 h*ng/mL Standard Deviation 9636.77	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	1302.7 h*ng/mL Standard Deviation 652.18	1571.3 h*ng/mL Standard Deviation 944.71	—
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	2223.2 h*ng/mL Standard Deviation 877.20	3213.9 h*ng/mL Standard Deviation 1221.71	—
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	31078.3 h*ng/mL Standard Deviation 16745.94	46810.1 h*ng/mL Standard Deviation 25249.07	—
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	45341.9 h*ng/mL Standard Deviation 8712.71	50471.2 h*ng/mL Standard Deviation 23077.43	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=17 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	3536.8 h*ng/mL Standard Deviation 2040.59	—	—
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	7716.6 h*ng/mL Standard Deviation 3534.76	—	—
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	71463.3 h*ng/mL Standard Deviation 28979.92	—	—
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	18460.1 h*ng/mL Standard Deviation 19999.95	—	—

PRIMARY outcome

Timeframe: 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.

Cmax is defined as the maximum concentration of drug.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	575.9 ng/mL Standard Deviation 487.66	976.8 ng/mL Standard Deviation 712.04	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	308.3 ng/mL Standard Deviation 132.60	538.3 ng/mL Standard Deviation 241.51	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	1750.0 ng/mL Standard Deviation 578.56	2721.4 ng/mL Standard Deviation 1452.86	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	1373.1 ng/mL Standard Deviation 496.37	1373.8 ng/mL Standard Deviation 550.23	—

PRIMARY outcome

Timeframe: 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.

Cmax is defined as the maximum concentration of drug.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	903.9 ng/mL Standard Deviation 598.55	1422.9 ng/mL Standard Deviation 1390.47	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	352.2 ng/mL Standard Deviation 127.83	509.1 ng/mL Standard Deviation 216.71	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	1727.0 ng/mL Standard Deviation 775.37	2645.0 ng/mL Standard Deviation 1482.10	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	2458.8 ng/mL Standard Deviation 437.54	2589.4 ng/mL Standard Deviation 1159.66	—

PRIMARY outcome

Timeframe: 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.

Cmax is defined as the maximum concentration of drug.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=17 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	2018.1 ng/mL Standard Deviation 1110.56	—	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	1021.6 ng/mL Standard Deviation 359.13	—	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	3570.0 ng/mL Standard Deviation 1325.31	—	—
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	903.4 ng/mL Standard Deviation 844.70	—	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	NA ng/mL Standard Deviation NA All values were below the limit of quantitation.	NA ng/mL Standard Deviation NA All values were below the limit of quantitation.	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	3.7 ng/mL Standard Deviation 7.88	20.8 ng/mL Standard Deviation 20.51	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	1023.0 ng/mL Standard Deviation 477.15	1736.1 ng/mL Standard Deviation 1110.41	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	759.1 ng/mL Standard Deviation 240.04	818.8 ng/mL Standard Deviation 323.67	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=9 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	NA ng/mL Standard Deviation NA All values were below the limit of quantitation.	NA ng/mL Standard Deviation NA All values were below the limit of quantitation.	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	2.3 ng/mL Standard Deviation 7.12	10.4 ng/mL Standard Deviation 11.07	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	952.5 ng/mL Standard Deviation 586.51	1356.0 ng/mL Standard Deviation 681.23	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	1567.5 ng/mL Standard Deviation 529.35	1968.6 ng/mL Standard Deviation 884.99	—

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=16 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	2.9 ng/mL Standard Deviation 1.57	—	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	59.3 ng/mL Standard Deviation 88.08	—	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	2568.2 ng/mL Standard Deviation 1106.81	—	—
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	705.0 ng/mL Standard Deviation 876.54	—	—

SECONDARY outcome

Timeframe: Posttreatment Week 4

Population: Full Analysis Set

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	40.0 percentage of participants Interval 12.2 to 73.8	60.0 percentage of participants Interval 26.2 to 87.8	100.0 percentage of participants Interval 81.5 to 100.0

SECONDARY outcome

Timeframe: Posttreatment Week 24

Population: Full Analysis Set

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	40.0 percentage of participants Interval 12.2 to 73.8	60.0 percentage of participants Interval 26.2 to 87.8	100.0 percentage of participants Interval 81.5 to 100.0

SECONDARY outcome

Timeframe: Up to Posttreatment Week 24

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 Participants LDV/SOF 90/400 mg FDC tablet for 12 weeks
Percentage of Participants With Overall Virologic Failure	50.0 percentage of participants	40.0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	885.0 h*ng/mL Standard Deviation 710.72	1607.7 h*ng/mL Standard Deviation 854.70	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	1973.3 h*ng/mL Standard Deviation 851.52	3965.7 h*ng/mL Standard Deviation 1900.25	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	31859.4 h*ng/mL Standard Deviation 12621.62	51989.6 h*ng/mL Standard Deviation 29461.91	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	22253.9 h*ng/mL Standard Deviation 6860.72	23595.5 h*ng/mL Standard Deviation 9636.77	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	1177.7 h*ng/mL Standard Deviation 674.86	1548.1 h*ng/mL Standard Deviation 955.12	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	1867.1 h*ng/mL Standard Deviation 839.39	3133.0 h*ng/mL Standard Deviation 1230.39	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	31078.3 h*ng/mL Standard Deviation 16745.94	46810.1 h*ng/mL Standard Deviation 25249.07	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	45341.9 h*ng/mL Standard Deviation 8712.71	50471.2 h*ng/mL Standard Deviation 23077.43	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=17 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	3519.3 h*ng/mL Standard Deviation 2045.64	—	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	7657.6 h*ng/mL Standard Deviation 3555.57	—	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	69177.7 h*ng/mL Standard Deviation 31267.56	—	—
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	18044.3 h*ng/mL Standard Deviation 20210.19	—	—

SECONDARY outcome

Timeframe: 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.

Clast is defined as the last observable concentration of drug.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	68.0 ng/mL Standard Deviation 100.22	21.3 ng/mL Standard Deviation 22.22	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	37.6 ng/mL Standard Deviation 18.84	35.8 ng/mL Standard Deviation 21.06	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	1023.0 ng/mL Standard Deviation 477.15	1736.1 ng/mL Standard Deviation 1110.41	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	759.1 ng/mL Standard Deviation 240.04	818.8 ng/mL Standard Deviation 323.67	—

SECONDARY outcome

Timeframe: 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.

Clast is defined as the last observable concentration of drug.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	100.7 ng/mL Standard Deviation 158.83	22.7 ng/mL Standard Deviation 30.15	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	72.2 ng/mL Standard Deviation 80.16	32.1 ng/mL Standard Deviation 22.04	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	952.5 ng/mL Standard Deviation 586.51	1412.9 ng/mL Standard Deviation 705.06	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	1741.3 ng/mL Standard Deviation 417.42	2040.9 ng/mL Standard Deviation 917.23	—

SECONDARY outcome

Timeframe: 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.

Clast is defined as the last observable concentration of drug.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=17 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	56.3 ng/mL Standard Deviation 216.91	—	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	70.5 ng/mL Standard Deviation 97.14	—	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	2570.6 ng/mL Standard Deviation 1071.71	—	—
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	700.6 ng/mL Standard Deviation 848.90	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	1.00 hours Interval 0.5 to 2.0	1.50 hours Interval 1.0 to 2.13	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	2.17 hours Interval 2.0 to 3.97	4.00 hours Interval 2.0 to 4.0	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	4.00 hours Interval 4.0 to 4.0	6.00 hours Interval 4.0 to 6.0	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	2.00 hours Interval 1.0 to 2.0	2.00 hours Interval 1.0 to 2.0	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	1.04 hours Interval 1.0 to 2.0	0.50 hours Interval 0.5 to 1.5	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	2.17 hours Interval 1.93 to 4.0	2.00 hours Interval 1.5 to 4.0	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	5.11 hours Interval 4.0 to 6.05	5.00 hours Interval 4.0 to 6.0	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	2.00 hours Interval 1.0 to 2.17	1.50 hours Interval 1.0 to 3.0	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=17 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	1.00 hours Interval 0.5 to 1.1	—	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	2.00 hours Interval 2.0 to 2.02	—	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	4.02 hours Interval 4.0 to 6.02	—	—
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	6.00 hours Interval 4.0 to 8.0	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	4.00 hours Interval 3.92 to 4.13	6.00 hours Interval 4.0 to 8.13	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	12.00 hours Interval 11.97 to 12.0	24.00 hours Interval 12.0 to 24.0	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	24.00 hours Interval 24.0 to 24.0	24.00 hours Interval 24.0 to 24.0	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	24.00 hours Interval 24.0 to 24.0	24.00 hours Interval 24.0 to 24.0	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	4.00 hours Interval 2.33 to 4.0	4.03 hours Interval 4.0 to 6.0	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	12.00 hours Interval 10.0 to 12.02	24.00 hours Interval 12.0 to 24.0	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	24.00 hours Interval 24.0 to 24.0	24.00 hours Interval 24.0 to 24.0	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	24.00 hours Interval 24.0 to 24.0	24.00 hours Interval 24.0 to 24.0	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=17 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	12.00 hours Interval 12.0 to 12.0	—	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	24.00 hours Interval 24.0 to 24.0	—	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	24.00 hours Interval 24.0 to 24.0	—	—
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	24.00 hours Interval 24.0 to 24.0	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	1.0419 1/hour Standard Deviation 0.28621	1.0155 1/hour Standard Deviation 0.33118	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	0.2078 1/hour Standard Deviation 0.04748	0.1771 1/hour Standard Deviation 0.05802	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	0.0275 1/hour Standard Deviation 0.01331	0.0273 1/hour Standard Deviation 0.01711	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	0.0165 1/hour Standard Deviation 0.00524	0.0141 1/hour Standard Deviation 0.00658	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	1.4002 1/hour Standard Deviation 0.29086	1.2154 1/hour Standard Deviation 0.24100	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	0.2232 1/hour Standard Deviation 0.05244	0.1818 1/hour Standard Deviation 0.06121	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	0.0332 1/hour Standard Deviation 0.01388	0.0313 1/hour Standard Deviation 0.02100	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	0.0124 1/hour Standard Deviation 0.00580	0.0085 1/hour Standard Deviation 0.00509	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=16 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	0.6033 1/hour Standard Deviation 0.24057	—	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	0.1705 1/hour Standard Deviation 0.04602	—	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	0.0214 1/hour Standard Deviation 0.01222	—	—
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	0.0305 1/hour Standard Deviation 0.01226	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) SOF	0.67 hours Interval 0.59 to 0.75	0.67 hours Interval 0.57 to 0.87	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-566500	3.31 hours Interval 2.95 to 3.98	3.88 hours Interval 3.17 to 4.44	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) GS-331007	30.53 hours Interval 19.14 to 43.25	29.05 hours Interval 17.29 to 35.15	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2) RBV	46.89 hours Interval 41.03 to 47.87	56.43 hours Interval 43.06 to 71.53	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=8 Participants SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) SOF	0.48 hours Interval 0.45 to 0.49	0.57 hours Interval 0.48 to 0.67	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-566500	3.03 hours Interval 2.72 to 3.96	3.88 hours Interval 2.93 to 4.79	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) GS-331007	22.03 hours Interval 18.76 to 27.96	33.54 hours Interval 13.61 to 45.15	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2) RBV	61.25 hours Interval 45.37 to 88.73	91.62 hours Interval 54.0 to 171.91	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=16 Participants SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) LDV/SOF 90/400 mg FDC tablet for 12 weeks
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) SOF	1.18 hours Interval 1.11 to 1.47	—	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-566500	4.02 hours Interval 3.57 to 4.68	—	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) GS-331007	39.30 hours Interval 30.38 to 54.89	—	—
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3) LDV	25.96 hours Interval 18.25 to 31.89	—	—

Adverse Events

SOF 200 mg + RBV 200 mg (Cohort 1)

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

SOF 400 mg + RBV 200 mg (Cohort 2)

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

LDV/SOF (Cohort 3)

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SOF 200 mg + RBV 200 mg (Cohort 1) n=10 participants at risk SOF 200 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	SOF 400 mg + RBV 200 mg (Cohort 2) n=10 participants at risk SOF 400 mg tablet once daily + RBV 200 mg tablet once daily for 24 weeks	LDV/SOF (Cohort 3) n=18 participants at risk LDV/SOF 90/400 mg FDC tablet for 12 weeks
Blood and lymphatic system disorders Anaemia	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	10.0% 1/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Cardiac disorders Angina unstable	10.0% 1/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Gastrointestinal disorders Haematemesis	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	10.0% 1/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
General disorders Non-cardiac chest pain	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	5.6% 1/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Infections and infestations Pneumonia	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	10.0% 1/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	5.6% 1/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	10.0% 1/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	5.6% 1/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Nervous system disorders Syncope	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	5.6% 1/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	11.1% 2/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.
Vascular disorders Hypotension	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	0.00% 0/10 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.	5.6% 1/18 • Up to end of treatment (Week 12 or Week 24) plus 30 days Safety Analysis Set: participants who took at least 1 dose of study drug.

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER