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
Results First Received: August 28, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Hepatitis C
HIV
Interventions: 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

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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.


Reporting Groups
  Description
Part A: SOF+EFV/FTC/TDF (Cohort 1) Sofosbuvir (SOF; 1 × 400 mg tablet or 2 × 200 mg tablets) + efavirenz (EFV) 600 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg tablet coadministered once daily for 7 days followed by EFV/FTC/TDF (600/200/300 mg) tablet once daily for 7 days.
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 + zidovudine (ZDV) 300 mg/lamivudine (3TC) 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.
Part A: SOF+RTV+ATV+FTC/TDF (Cohort 3) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + atazanavir (ATV) 400 mg tablet boosted with ritonavir (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.
Part A: SOF+RTV+DRV+FTC/TDF (Cohort 4) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + darunavir (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.
Part A: SOF+RAL+FTC/TDF (Cohort 5) SOF (1 × 400 mg tablet or 2 × 200 mg tablets) once daily + raltegravir (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.
Part B: SOF+PEG+RBV SOF 400 mg tablet once daily + pegylated interferon alpha (PEG) 180 μg subcutaneous injection once weekly + weight-based ribavirin (RBV; 1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks.

Participant Flow for 2 periods

Period 1:   Part A
    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  
STARTED     12     4     8     7     7     0  
COMPLETED     11 [1]   4 [2]   8 [1]   7 [3]   7 [4]   0  
NOT COMPLETED     1     0     0     0     0     0  
Withdrawal by Subject                 1                 0                 0                 0                 0                 0  
[1] 3 participants from this group continued in the Part B: SOF+PEG+RBV group.
[2] No participants from this group continued in the Part B: SOF+PEG+RBV group.
[3] 2 participants from this group continued in the Part B: SOF+PEG+RBV group.
[4] 1 participant from this group continued in the Part B: SOF+PEG+RBV group.

Period 2:   Part B
    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  
STARTED     0     0     0     0     0     23 [1]
COMPLETED     0     0     0     0     0     19  
NOT COMPLETED     0     0     0     0     0     4  
Withdrawal by Subject                 0                 0                 0                 0                 0                 1  
Lack of Efficacy                 0                 0                 0                 0                 0                 2  
Lost to Follow-up                 0                 0                 0                 0                 0                 1  
[1] 9 participants in this group transferred from a Part A cohort, and 14 participants joined the study.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: participants who enrolled and received at least one dose of study drug(s)

Reporting Groups
  Description
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.
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.
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.
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.
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.
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.

Total Total of all reporting groups

Baseline Measures
    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  
Number of Participants  
[units: participants]
  12     4     8     7     7     14     52  
Age  
[units: years]
Mean ± Standard Deviation
  54  ± 10.1     58  ± 5.3     47  ± 6.4     47  ± 3.8     46  ± 10.3     46  ± 8.7     47  ± 7.2  
Gender  
[units: participants]
             
Female     2     0     1     1     1     3     8  
Male     10     4     7     6     6     11     44  
Ethnicity (NIH/OMB)  
[units: participants]
             
Hispanic or Latino     12     4     7     7     7     14     51  
Not Hispanic or Latino     0     0     1     0     0     0     1  
Unknown or Not Reported     0     0     0     0     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
             
White     8     2     4     3     7     11     35  
Black or African American     4     2     4     4     0     3     17  
Study-Specific Measure [1]
[units: participants]
             
Genotype 1A     5     1     5     5     6     9     31  
Genotype 1B     5     1     1     0     0     2     9  
Genotype 2B     1     1     2     0     0     0     4  
Genotype 3A     0     1     0     2     1     2     6  
Genotype 4     1     0     0     0     0     0     1  
Genotype 4A/4C/4D     0     0     0     0     0     1     1  
[1] There are variations of HCV which are all similar enough to be called HCV, but are distinct enough to be referred to as HCV genotypes.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   Part B: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)   [ Time Frame: Posttreatment Week 12 ]

4.  Primary:   Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)   [ Time Frame: Up to 12 weeks ]

5.  Secondary:   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 ]

6.  Secondary:   Part B: Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse   [ Time Frame: Posttreatment Weeks 4 and 24 ]

7.  Other Pre-specified:   Part B: On-treatment HCV RNA   [ Time Frame: Up to 8 weeks ]

8.  Other Pre-specified:   Part B: On-treatment HIV RNA   [ Time Frame: Up to 8 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


No publications provided


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