Part A: Drug Interaction Study of Sofosbuvir and Antiretroviral Therapy (ART) Combinations in HIV and Hepatitis C Virus (HCV) Co-infected Patients. Part B: Efficacy and Safety of Sofosbuvir for 12 Weeks in HIV/HCV Co-infected Patients.

Phase 1

Completed

Conditions: Hepatitis C
HIV

Interventions: Drug: SOF
Drug: ATV
Drug: EFV
Drug: EFV/FTC/TDF
Drug: PEG
Drug: RAL
Drug: ZDV/3TC
Drug: Ritonavir
Drug: RBV
Drug: FTC/TDF
Drug: DRV

Registration Number: NCT01565889

Lead Sponsor: Gilead Sciences

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 52

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: SOF+EFV/FTC/TDF (Cohort 1)	SOF	Participants with a prestudy regimen of EFV/FTC/TDF will receive SOF+EFV/FTC/TDF FDC for 7 days, followed by EFV/FTC/TDF FDC (or EFV+FTC/TDF) for 7 days, coadministered once daily in the evening under fasting conditions.
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)	ATV	Participants with a prestudy regimen of RTV+ATV+FTC/TDF will receive SOF+RTV+ATV+FTC/TDF for 7 days followed by RTV+ATV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)	FTC/TDF	Participants with a prestudy regimen of RTV+ATV+FTC/TDF will receive SOF+RTV+ATV+FTC/TDF for 7 days followed by RTV+ATV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)	DRV	Participants with a prestudy regimen of RTV+DRV+FTC/TDF will receive SOF+RTV+DRV+FTC/TDF for 7 days followed by RTV+DRV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part A: SOF+EFV+ZDV/3TC (Cohort 2)	EFV	Participants with a prestudy regimen of EFV+ZDV/3TC will receive SOF+EFV+ZDV/3TC for 7 days followed by EFV+ZDV/3TC for 7 days. Sofosbuvir and EFV will be administered once daily in the evening under fasting conditions; ZDV/3TC will be administered twice daily, in the morning without regard to food and in the evening on an empty stomach.
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)	SOF	Participants with a prestudy regimen of RTV+ATV+FTC/TDF will receive SOF+RTV+ATV+FTC/TDF for 7 days followed by RTV+ATV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)	SOF	Participants with a prestudy regimen of RTV+DRV+FTC/TDF will receive SOF+RTV+DRV+FTC/TDF for 7 days followed by RTV+DRV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)	FTC/TDF	Participants with a prestudy regimen of RTV+DRV+FTC/TDF will receive SOF+RTV+DRV+FTC/TDF for 7 days followed by RTV+DRV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part B: SOF+PEG+RBV	SOF	Participants will receive SOF+PEG+RBV for 12 weeks.
Part A: SOF+RAL+FTC/TDF (Cohort 5)	RAL	Participants with a prestudy regimen of RAL+FTC/TDF will receive SOF+RAL+FTC/TDF for 7 days followed by RAL+FTC/TDF for 7 days. Sofosbuvir and FTC/TDF will be administered once daily in the morning with food; RAL will be administered twice daily, in the morning with food and in the evening without regard to food.
Part A: SOF+EFV+ZDV/3TC (Cohort 2)	SOF	Participants with a prestudy regimen of EFV+ZDV/3TC will receive SOF+EFV+ZDV/3TC for 7 days followed by EFV+ZDV/3TC for 7 days. Sofosbuvir and EFV will be administered once daily in the evening under fasting conditions; ZDV/3TC will be administered twice daily, in the morning without regard to food and in the evening on an empty stomach.
Part A: SOF+EFV+ZDV/3TC (Cohort 2)	ZDV/3TC	Participants with a prestudy regimen of EFV+ZDV/3TC will receive SOF+EFV+ZDV/3TC for 7 days followed by EFV+ZDV/3TC for 7 days. Sofosbuvir and EFV will be administered once daily in the evening under fasting conditions; ZDV/3TC will be administered twice daily, in the morning without regard to food and in the evening on an empty stomach.
Part A: SOF+RAL+FTC/TDF (Cohort 5)	SOF	Participants with a prestudy regimen of RAL+FTC/TDF will receive SOF+RAL+FTC/TDF for 7 days followed by RAL+FTC/TDF for 7 days. Sofosbuvir and FTC/TDF will be administered once daily in the morning with food; RAL will be administered twice daily, in the morning with food and in the evening without regard to food.
Part A: SOF+EFV/FTC/TDF (Cohort 1)	EFV/FTC/TDF	Participants with a prestudy regimen of EFV/FTC/TDF will receive SOF+EFV/FTC/TDF FDC for 7 days, followed by EFV/FTC/TDF FDC (or EFV+FTC/TDF) for 7 days, coadministered once daily in the evening under fasting conditions.
Part A: SOF+RAL+FTC/TDF (Cohort 5)	FTC/TDF	Participants with a prestudy regimen of RAL+FTC/TDF will receive SOF+RAL+FTC/TDF for 7 days followed by RAL+FTC/TDF for 7 days. Sofosbuvir and FTC/TDF will be administered once daily in the morning with food; RAL will be administered twice daily, in the morning with food and in the evening without regard to food.
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3)	Ritonavir	Participants with a prestudy regimen of RTV+ATV+FTC/TDF will receive SOF+RTV+ATV+FTC/TDF for 7 days followed by RTV+ATV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4)	Ritonavir	Participants with a prestudy regimen of RTV+DRV+FTC/TDF will receive SOF+RTV+DRV+FTC/TDF for 7 days followed by RTV+DRV+FTC/TDF for 7 days coadministered once daily in the morning with food.
Part B: SOF+PEG+RBV	RBV	Participants will receive SOF+PEG+RBV for 12 weeks.
Part B: SOF+PEG+RBV	PEG	Participants will receive SOF+PEG+RBV for 12 weeks.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.