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.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01565889
First received: March 27, 2012
Last updated: September 25, 2014
Last verified: September 2014

March 27, 2012
September 25, 2014
March 2012
August 2013   (final data collection date for primary outcome measure)
  • 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.
Evaluate whether PSI-7977 will significantly influence the PK parameters of ATV/r, EFV, TDF, FTC, ZDV or 3TC in healthy HIV/HCV co-infected subjects. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01565889 on ClinicalTrials.gov Archive Site
  • 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.

  • Evaluate whether ATV/r, EFV, TDF, FTC, ZDV or 3TC will significantly affect the pharmacokinetic parameters of PSI-7977 and metabolites in healthy HIV/HCV co-infected subjects compared with historical data from HCV mono-infected subjects. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • Evaluate the viral kinetics of the effect of PSI-7977 on HCV RNA in HIV/HCV co-infected subjects receiving pre-specified ART regimens for 7 days. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of 7 days of dosing of PSI-7977 in combination with ATV/r, EFV, TDF, FTC, ZDV or 3TC in healthy HIV/HCV co-infected subjects. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • 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.
Not Provided
 
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.
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.

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C
  • HIV
  • 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®
  • 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®
  • 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®
  • Drug: DRV
    Darunavir (DRV) 800 mg (2 × 400 mg tablets) administered orally once daily
  • Drug: RAL
    Raltegravir (RAL) 400 mg administered administered orally twice daily
  • 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®
  • 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.
    Interventions:
    • Drug: SOF
    • Drug: EFV/FTC/TDF
  • 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.
    Interventions:
    • Drug: SOF
    • Drug: EFV
    • Drug: ZDV/3TC
  • 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.
    Interventions:
    • Drug: SOF
    • Drug: ATV
    • Drug: Ritonavir
    • Drug: FTC/TDF
  • 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.
    Interventions:
    • Drug: SOF
    • Drug: Ritonavir
    • Drug: FTC/TDF
    • Drug: DRV
  • 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.
    Interventions:
    • Drug: SOF
    • Drug: FTC/TDF
    • Drug: RAL
  • Experimental: Part B: SOF+PEG+RBV
    Participants will receive SOF+PEG+RBV for 12 weeks.
    Interventions:
    • Drug: SOF
    • Drug: PEG
    • Drug: RBV
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
November 2013
August 2013   (final data collection date for primary outcome measure)

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
Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Puerto Rico
 
NCT01565889
P7977-1910
No
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Anuj Gaggar, MD/PhD Gilead Sciences
Gilead Sciences
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP