Hepatitis C, HIV
Conditions
Brief summary
This study consists of 2 parts, Part A and Part B. Part A, the Phase 1 drug interaction/early viral kinetic study, will evaluate the effect of selected antiretroviral therapies on the safety, viral kinetics, and pharmacokinetics of sofosbuvir (GS-7977; PSI-7977) and its metabolites in participants with HIV and hepatitis C virus (HCV) coinfection. Part B, the Phase 2 treatment study, will investigate the efficacy and safety of sofosbuvir, pegylated interferon alpha (PEG) and ribavirin (RBV) in participants with HIV/HCV coinfection.
Interventions
DRUGSOF
Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily
DRUGEFV/FTC/TDF
Efavirenz (EFV) 600 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination (FDC) tablet administered orally once daily
DRUGEFV
Efavirenz (EFV) 600 mg tablet administered orally once daily
DRUGZDV/3TC
Zidovudine (ZDV) 300 mg/lamivudine (3TC) 150 mg FDC tablet administered orally twice daily
DRUGATV
Atazanavir (ATV) 400 mg tablet administered orally once daily
DRUGRitonavir
Ritonavir (RTV) 100 mg tablet administered orally once daily
DRUGFTC/TDF
FTC/TDF (200/300 mg) FDC tablet administered orally once daily
DRUGDRV
Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily
DRUGRAL
Raltegravir (RAL) 400 mg administered administered orally twice daily
DRUGPEG
Pegylated interferon alfa (PEG) 180 μg administered once weekly by subcutaneous injection
DRUGRBV
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Healthy according to medical history and physical examination with exception of HCV and HIV diagnoses * Confirmation of Chronic HCV infection * Confirmation of Chronic HIV-1 infection * On a stable protocol approved HIV antiretroviral (ARV) regimen with undetectable HIV-RNA * Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication * Subjects must be naive to treatment for chronic HCV infection
Exclusion criteria
* Known or suspected cirrhosis * History of any other clinically significant chronic liver disease * A history consistent with decompensated liver disease. * Use of any prohibited medications as defined by the protocol * Pregnant or nursing female or male with pregnant female partner * Contraindication to PEG or RBV therapy (for Part B) * Clinically relevant drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | Up to 12 weeks | The percentage of participants discontinuing any study drug due to an adverse event was summarized. |
| Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose | AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Data for this outcome measure were collected for participants in Part A only. |
| Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose | Cmax: maximum observed concentration of drug in plasma. Data for this outcome measure were collected for participants in Part A only. |
| Part B: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. Data for this outcome measure were collected for participants in Part B only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR24 was defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. Data for this outcome measure were collected for participants in Part B only. |
| Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Posttreatment Weeks 4 and 24 | Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA \> LLOQ) on treatment after having previously had undetectable HCV RNA levels (HCV RNA \< LLOQ) while on treatment. Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) at end of treatment, but did not achieve an SVR. Data for this outcome measure were collected for participants in Part B only. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part B: On-treatment HCV RNA | Up to 8 weeks | Data for this outcome measure were collected for participants in Part B only. |
| Part B: On-treatment HIV RNA | Up to 8 weeks | Data for this outcome measure were collected for participants in Part B only. |
Countries
Puerto Rico
Participant flow
Recruitment details
52 participants were enrolled at one study site in Puerto Rico, a commonwealth of the United States (US). The first participant was screened on 27 February 2012. The last participant observation occurred on 10 December 2013.
Pre-assignment details
Part A: 52 participants were screened; 38 were enrolled and treated, and comprise the Part A Safety Analysis Set (SAS) and Part A Full Analysis Set (FAS). Part B: 42 participants were screened; 23 were enrolled and treated (9 from Part A and 14 who joined the study), and comprise the Part B SAS and Part B FAS.
Participants by arm
| Arm | Count |
|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) + EFV/FTC/TDF (600/200/300 mg) tablet coadministered once daily for 7 days followed by EFV/FTC/TDF (600/200/300 mg) tablet once daily for 7 days. | 12 |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + EFV 600 mg tablet once daily + ZDV/3TC (300/150 mg) tablet twice daily for 7 days followed by EFV 600 mg tablet once daily + ZDV/3TC (300/150 mg) tablet twice daily for 7 days. | 4 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + ATV 400 mg tablet boosted with RTV 100 mg tablet + FTC/TDF (200/300 mg) tablet coadministered once daily for 7 days followed by ATV 400 mg tablet + RTV 100 mg tablet + FTC/TDF (200/300 mg) tablet coadministered once daily for 7 days. | 8 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + DRV (800 mg; 2 × 400 mg tablets) boosted with RTV 100 mg tablet + FTC/TDF (200/300 mg) tablet coadministered once daily for 7 days followed by DRV (800 mg; 2 x 400 mg tablets) + RTV 100 mg tablet + FTC/TDF (200/300 mg) tablet coadministered once daily for 7 days. | 7 |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + RAL 400 mg tablet twice daily + FTC/TDF (200/300 mg) tablet once daily for 7 days followed by RAL 400 mg twice daily + FTC/TDF (200/300 mg) tablet once daily for 7 days. | 7 |
| Part B: SOF+PEG+RBV SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.
This reporting group presents data for those participants who joined the study for Part B only. | 14 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part A | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Part B | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 2 |
| Part B | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Part B | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part B: SOF+PEG+RBV | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 10.1 | 58 years STANDARD_DEVIATION 5.3 | 47 years STANDARD_DEVIATION 6.4 | 47 years STANDARD_DEVIATION 3.8 | 46 years STANDARD_DEVIATION 10.3 | 46 years STANDARD_DEVIATION 8.7 | 47 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 4 Participants | 7 Participants | 7 Participants | 7 Participants | 14 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotype Genotype 1A | 5 participants | 1 participants | 5 participants | 5 participants | 6 participants | 9 participants | 31 participants |
| HCV Genotype Genotype 1B | 5 participants | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants | 9 participants |
| HCV Genotype Genotype 2B | 1 participants | 1 participants | 2 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| HCV Genotype Genotype 3A | 0 participants | 1 participants | 0 participants | 2 participants | 1 participants | 2 participants | 6 participants |
| HCV Genotype Genotype 4 | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| HCV Genotype Genotype 4A/4C/4D | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 4 participants | 2 participants | 4 participants | 4 participants | 0 participants | 3 participants | 17 participants |
| Race/Ethnicity, Customized White | 8 participants | 2 participants | 4 participants | 3 participants | 7 participants | 11 participants | 35 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 7 Participants | 6 Participants | 6 Participants | 11 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 12 | 0 / 4 | 0 / 8 | 2 / 7 | 1 / 7 | 16 / 23 |
| serious Total, serious adverse events | 0 / 12 | 0 / 4 | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 23 |
Outcome results
Primary
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
The percentage of participants discontinuing any study drug due to an adverse event was summarized.
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who received at least 1 dose of study drug(s)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 0 percentage of participants |
| Part B: SOF+PEG+RBV | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 8.7 percentage of participants |
Primary
Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Data for this outcome measure were collected for participants in Part A only.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Population: Pharmacokinetics (PK) Analysis Set: participants with evaluable PK profiles who enrolled into Part A of the study and received study drug.~Participants in the PK Analysis Set with available data were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of EFV (AUCtau at Day 7) | 95094.4 h*ng/mL | Standard Deviation 71267.91 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of SOF (AUCtau at Day 7) | 867.5 h*ng/mL | Standard Deviation 460.34 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of TFV (AUCtau at Day 7) | 2351.2 h*ng/mL | Standard Deviation 960.74 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of FTC (AUCtau at Day 7) | 10144.8 h*ng/mL | Standard Deviation 2832.23 |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of FTC (AUCtau at Day 7) | NA h*ng/mL | — |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of TFV (AUCtau at Day 7) | NA h*ng/mL | — |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of SOF (AUCtau at Day 7) | 627.6 h*ng/mL | Standard Deviation 315.87 |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of EFV (AUCtau at Day 7) | 53770.7 h*ng/mL | Standard Deviation 39263.9 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of FTC (AUCtau at Day 7) | 11564.9 h*ng/mL | Standard Deviation 1739.26 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of SOF (AUCtau at Day 7) | 2269.4 h*ng/mL | Standard Deviation 567.58 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of TFV (AUCtau at Day 7) | 3793.0 h*ng/mL | Standard Deviation 835.11 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of EFV (AUCtau at Day 7) | NA h*ng/mL | — |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of SOF (AUCtau at Day 7) | 1421.5 h*ng/mL | Standard Deviation 415.1 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of TFV (AUCtau at Day 7) | 3996.8 h*ng/mL | Standard Deviation 1665.17 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of EFV (AUCtau at Day 7) | NA h*ng/mL | — |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of FTC (AUCtau at Day 7) | 13091.2 h*ng/mL | Standard Deviation 4093.09 |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of EFV (AUCtau at Day 7) | NA h*ng/mL | — |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of SOF (AUCtau at Day 7) | 1687.1 h*ng/mL | Standard Deviation 573.42 |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of TFV (AUCtau at Day 7) | 2657.1 h*ng/mL | Standard Deviation 751.31 |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 | Pharmacokinetics of FTC (AUCtau at Day 7) | 10622.8 h*ng/mL | Standard Deviation 815.24 |
Primary
Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7
Cmax: maximum observed concentration of drug in plasma. Data for this outcome measure were collected for participants in Part A only.
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose
Population: Participants in the PK Analysis Set with available data were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of TFV (Cmax at Day 7) | 372.5 ng/mL | Standard Deviation 208.71 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of SOF (Cmax at Day 7) | 635.0 ng/mL | Standard Deviation 344.19 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of EFV (Cmax at Day 7) | 5423.8 ng/mL | Standard Deviation 3283.86 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of FTC (Cmax at Day 7) | 1533.1 ng/mL | Standard Deviation 829.88 |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of EFV (Cmax at Day 7) | 3469.5 ng/mL | Standard Deviation 1707.54 |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of SOF (Cmax at Day 7) | 285.1 ng/mL | Standard Deviation 62.28 |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of TFV (Cmax at Day 7) | NA ng/mL | — |
| Part A: SOF+EFV+ZDV/3TC (Cohort 2) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of FTC (Cmax at Day 7) | NA ng/mL | — |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of SOF (Cmax at Day 7) | 1228.9 ng/mL | Standard Deviation 474.93 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of FTC (Cmax at Day 7) | 1797.9 ng/mL | Standard Deviation 232.54 |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of EFV (Cmax at Day 7) | NA ng/mL | — |
| Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of TFV (Cmax at Day 7) | 519.8 ng/mL | Standard Deviation 119.89 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of SOF (Cmax at Day 7) | 828.2 ng/mL | Standard Deviation 351.41 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of FTC (Cmax at Day 7) | 1808.2 ng/mL | Standard Deviation 530.1 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of TFV (Cmax at Day 7) | 441.8 ng/mL | Standard Deviation 134.13 |
| Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of EFV (Cmax at Day 7) | NA ng/mL | — |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of FTC (Cmax at Day 7) | 2079.5 ng/mL | Standard Deviation 434.32 |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of SOF (Cmax at Day 7) | 1189.2 ng/mL | Standard Deviation 483.83 |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of EFV (Cmax at Day 7) | NA ng/mL | — |
| Part A: SOF+RAL+FTC/TDF (Cohort 5) | Part A: Plasma Pharmacokinetics of SOF, EFV, TFV, and FTC: Cmax at Day 7 | Pharmacokinetics of TFV (Cmax at Day 7) | 388.1 ng/mL | Standard Deviation 118.53 |
Primary
Part B: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. Data for this outcome measure were collected for participants in Part B only.
Time frame: Posttreatment Week 12
Population: Part B Full Analysis Set: participants enrolled into Part B of the study and dosed with at least 1 dose of study drug(s)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 91.3 percentage of participants |
Secondary
Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse
Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA \> LLOQ) on treatment after having previously had undetectable HCV RNA levels (HCV RNA \< LLOQ) while on treatment. Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA \< LLOQ) at end of treatment, but did not achieve an SVR. Data for this outcome measure were collected for participants in Part B only.
Time frame: Posttreatment Weeks 4 and 24
Population: Part B Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral breakthrough | 0 percentage of participants |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse | Viral relapse | 8.7 percentage of participants |
Secondary
Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 was defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. Data for this outcome measure were collected for participants in Part B only.
Time frame: Posttreatment Weeks 4 and 24
Population: Part B Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 91.3 percentage of participants |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 91.3 percentage of participants |
Other Pre-specified
Part B: On-treatment HCV RNA
Data for this outcome measure were collected for participants in Part B only.
Time frame: Up to 8 weeks
Population: Part B Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HCV RNA | Week 1 (n = 20) | 1.65 log10 IU/mL | Standard Deviation 0.425 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HCV RNA | Week 2 (n = 22) | 1.38 log10 IU/mL | Standard Deviation 0 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HCV RNA | Week 4 (n = 23) | 1.38 log10 IU/mL | Standard Deviation 0 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HCV RNA | Week 6 (n = 23) | 1.38 log10 IU/mL | Standard Deviation 0 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HCV RNA | Week 8 (n = 21) | 1.38 log10 IU/mL | Standard Deviation 0 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HCV RNA | Baseline (n = 23) | 6.59 log10 IU/mL | Standard Deviation 0.872 |
Other Pre-specified
Part B: On-treatment HIV RNA
Data for this outcome measure were collected for participants in Part B only.
Time frame: Up to 8 weeks
Population: Part B Safety Analysis Set: participants enrolled in Part B and received at least one dose of study drug(s).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HIV RNA | Baseline (n = 23) | 25 copies/mL | Standard Deviation 16.4 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HIV RNA | Week 1 (n = 20) | 20 copies/mL | Standard Deviation 4.1 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HIV RNA | Week 2 (n = 22) | 20 copies/mL | Standard Deviation 3 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HIV RNA | Week 4 (n = 22) | 19 copies/mL | Standard Deviation 0 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HIV RNA | Week 6 (n = 22) | 19 copies/mL | Standard Deviation 0 |
| Part A: SOF+EFV/FTC/TDF (Cohort 1) | Part B: On-treatment HIV RNA | Week 8 (n = 21) | 19 copies/mL | Standard Deviation 0 |