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. - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C HIV	Drug: SOF Drug: EFV/FTC/TDF Drug: EFV Drug: ZDV/3TC Drug: ATV Drug: Ritonavir Drug: FTC/TDF Drug: DRV Drug: RAL Drug: PEG Drug: RBV	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Part A: Drug Interaction Study Between GS-7977 and Antiretroviral Therapy (ARV) Combinations of Efavirenz, Tenofovir and Emtricitabine; Efavirenz, Zidovudine and Lamivudine; Atazanavir/Ritonavir, Tenofovir and Emtricitabine; Darunavir/Ritonavir, Tenofovir and Emtricitabine; Raltegravir, Tenofovir and Emtricitabine in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) Co-infected Patients. Part B: A Phase 2, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 With Peginterferon Alfa 2a and Ribavirin for 12 Weeks in Treatment-Naïve HIV/HCV Co-infected Patients.

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions HIV/AIDS Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Zidovudine Ribavirin Lamivudine Emtricitabine Efavirenz Ritonavir Peginterferon Alfa-2a Darunavir Sofosbuvir

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Part A: Plasma Pharmacokinetics of SOF, EFV, Tenofovir (TFV), and FTC: AUCtau at Day 7 [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose ] [ Designated as safety issue: No ]
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 [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours postdose ] [ Designated as safety issue: No ]
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) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
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.
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
The percentage of participants discontinuing any study drug due to an adverse event was summarized.

Secondary Outcome Measures:

Part B: Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
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 [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
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 Outcome Measures:

Part B: On-treatment HCV RNA [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
Data for this outcome measure were collected for participants in Part B only.
Part B: On-treatment HIV RNA [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
Data for this outcome measure were collected for participants in Part B only.


Enrollment:	52
Study Start Date:	March 2012
Study Completion Date:	November 2013
Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part A: SOF+EFV/FTC/TDF (Cohort 1) 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.	Drug: SOF Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: EFV/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 Other Name: Atripla®
Experimental: Part A: SOF+EFV+ZDV/3TC (Cohort 2) 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.	Drug: SOF Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: EFV Efavirenz (EFV) 600 mg tablet administered orally once daily Other Name: Sustiva® Drug: ZDV/3TC Zidovudine (ZDV) 300 mg/lamivudine (3TC) 150 mg FDC tablet administered orally twice daily Other Name: Combivir®
Experimental: Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) 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.	Drug: SOF Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: ATV Atazanavir (ATV) 400 mg tablet administered orally once daily Drug: Ritonavir Ritonavir (RTV) 100 mg tablet administered orally once daily Drug: FTC/TDF FTC/TDF (200/300 mg) FDC tablet administered orally once daily Other Name: Truvada®
Experimental: Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) 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.	Drug: SOF Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: Ritonavir Ritonavir (RTV) 100 mg tablet administered orally once daily Drug: FTC/TDF FTC/TDF (200/300 mg) FDC tablet administered orally once daily Other Name: Truvada® Drug: DRV Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily
Experimental: Part A: SOF+RAL+FTC/TDF (Cohort 5) 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.	Drug: SOF Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: FTC/TDF FTC/TDF (200/300 mg) FDC tablet administered orally once daily Other Name: Truvada® Drug: RAL Raltegravir (RAL) 400 mg administered administered orally twice daily
Experimental: Part B: SOF+PEG+RBV Participants will receive SOF+PEG+RBV for 12 weeks.	Drug: SOF Sofosbuvir (SOF) 400 mg (1 × 400 mg tablet or 2 × 200 mg tablets) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: PEG Pegylated interferon alfa (PEG) 180 μg administered once weekly by subcutaneous injection Other Name: Pegasys® Drug: RBV 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) Other Name: Ribasphere®

Eligibility


Ages Eligible for Study:	21 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565889

Locations


Puerto Rico
Fundacion de Investigacion de Diego
San Juan, Puerto Rico, 00927

Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	Anuj Gaggar, MD/PhD	Gilead Sciences

More Information


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01565889 History of Changes
Other Study ID Numbers:	P7977-1910
Study First Received:	March 27, 2012
Results First Received:	August 28, 2014
Last Updated:	September 25, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Ritonavir Darunavir Tenofovir Zidovudine	Emtricitabine Lamivudine Efavirenz Peginterferon alfa-2a Sofosbuvir HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016