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Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01818596
Recruitment Status : Completed
First Posted : March 26, 2013
Results First Posted : February 18, 2016
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HIV
HIV Infections
Intervention Drug: E/C/F/TAF
Enrollment 252
Recruitment Details Participants were enrolled at study sites in North America, Australia, Asia, and Europe. The first participant was screened on 27 March 2013. The last study visit occurred on 18 July 2018.
Pre-assignment Details 380 participants were screened.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) fixed-dose combination (FDC) tablet administered orally once daily with food for up to 240 weeks in antiretroviral treatment (ART)-experienced participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Period Title: Overall Study
Started 246 6
Completed 215 6
Not Completed 31 0
Reason Not Completed
Enrolled but Not Treated             4             0
Adverse Event             7             0
Death             3             0
Investigator's Discretion             4             0
Protocol Violation             1             0
Withdrew Consent             5             0
Lost to Follow-up             7             0
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive) Total
Hide Arm/Group Description E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants Total of all reporting groups
Overall Number of Baseline Participants 242 6 248
Hide Baseline Analysis Population Description
Safety Analysis Set: participants were enrolled and received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 242 participants 6 participants 248 participants
58  (9.9) 55  (7.1) 58  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 6 participants 248 participants
Female
50
  20.7%
0
   0.0%
50
  20.2%
Male
192
  79.3%
6
 100.0%
198
  79.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 242 participants 6 participants 248 participants
Asian
34
  14.0%
1
  16.7%
35
  14.1%
American Indian or Alaska Native
1
   0.4%
0
   0.0%
1
   0.4%
Black or African American
44
  18.2%
3
  50.0%
47
  19.0%
Native Hawaiian or Pacific Islander
2
   0.8%
0
   0.0%
2
   0.8%
White
152
  62.8%
2
  33.3%
154
  62.1%
Other
7
   2.9%
0
   0.0%
7
   2.8%
Not Permitted
2
   0.8%
0
   0.0%
2
   0.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 242 participants 6 participants 248 participants
Hispanic or Latino
31
  12.8%
1
  16.7%
32
  12.9%
Not Hispanic or Latino
209
  86.4%
5
  83.3%
214
  86.3%
Not Permitted
2
   0.8%
0
   0.0%
2
   0.8%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 242 participants 6 participants 248 participants
United States
166
  68.6%
5
  83.3%
171
  69.0%
United Kingdom
5
   2.1%
0
   0.0%
5
   2.0%
Thailand
30
  12.4%
1
  16.7%
31
  12.5%
Spain
13
   5.4%
0
   0.0%
13
   5.2%
Netherlands
2
   0.8%
0
   0.0%
2
   0.8%
Dominican Republic
6
   2.5%
0
   0.0%
6
   2.4%
Mexico
2
   0.8%
0
   0.0%
2
   0.8%
Australia
12
   5.0%
0
   0.0%
12
   4.8%
France
6
   2.5%
0
   0.0%
6
   2.4%
1.Primary Outcome
Title Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
Hide Description eGFR is a measurement of the kidney's ability to filter blood.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set (enrolled and received at least 1 dose of study drug) with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Baseline Number Analyzed 242 participants 6 participants
55.6
(45.7 to 62.4)
60.2
(45.0 to 63.2)
Change at Week 24 Number Analyzed 233 participants 6 participants
-0.4
(-4.7 to 4.5)
-0.3
(-3.6 to 1.3)
2.Primary Outcome
Title Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24
Hide Description eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline Number Analyzed 241 participants 6 participants
69.7
(55.9 to 82.7)
70.2
(64.0 to 100.8)
Change at Week 24 Number Analyzed 231 participants 6 participants
3.8
(-4.8 to 11.2)
3.9
(-3.3 to 13.2)
3.Primary Outcome
Title Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
Hide Description eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.
Time Frame Baseline; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline Number Analyzed 242 participants 6 participants
54.1
(46.0 to 62.8)
54.4
(41.7 to 81.4)
Change at Week 24 Number Analyzed 233 participants 6 participants
-1.8
(-6.1 to 4.9)
-2.6
(-11.1 to -0.9)
4.Secondary Outcome
Title Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy
Hide Description aGFR was directly measured using iohexol plasma clearance (CLiohexol).
Time Frame Baseline; Week 2, 4, or 8; Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Pharmacodynamic (PD) Substudy Analysis Set (enrolled in the pharmacokinetic (PK)/PD substudy, received at least 1 dose of study drug, and had baseline and at least 1 postbaseline assessment for aGFR assessed by CLiohexol) with available data at the respective time point were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: mL/min
Baseline Number Analyzed 32 participants
60.1  (19.06)
Change at Week 2, 4, or 8 Number Analyzed 32 participants
-0.6  (8.45)
Change at Week 24 Number Analyzed 30 participants
1.4  (9.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Substudy Participants
Comments Comparison is made between the baseline value and the value from the Week 2, 4, or 8 visit and presented as a geometric least squares mean (GLSM) ratio with 90% confidence interval (CI). Postbaseline value and baseline value were used as test and reference, respectively.
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments 30 participants with evaluable aGFR (measured by iohexol clearance) in either cohort would provide at least 90% power to show that aGFR change is < 20% after participants were administered E/C/F/TAF. In this sample size/power computation, it was assumed that the intra-participant variation for aGFR is 0.17 mL/min on natural logarithm scale and a clinical meaningful boundary in aGFR change is 80% to 125%.
Method of Estimation Estimation Parameter Difference in GLSM Ratio
Estimated Value 98.94
Confidence Interval (2-Sided) 90%
93.71 to 104.46
Estimation Comments A parametric analysis of variance model using a mixed-effects model with repeated statement was fitted to the natural logarithm transferred aGFR obtained at postbaseline visits and baseline.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Substudy Participants
Comments Comparison is made between the baseline value and the value from the Week 24 visit and presented as a GLSM ratio with 90% CI. Week 24 value and baseline value were used as test and reference, respectively.
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments 30 participants with evaluable aGFR (measured by iohexol clearance) in either cohort would provide at least 90% power to show that aGFR change is < 20% after participants were administered E/C/F/TAF. In this sample size/power computation, it was assumed that the intra-participant variation for aGFR is 0.17 mL/min on natural logarithm scale and a clinical meaningful boundary in aGFR change is 80% to 125%.
Method of Estimation Estimation Parameter Difference in GLSM Ratio
Estimated Value 102.66
Confidence Interval (2-Sided) 90%
97.11 to 108.53
Estimation Comments A parametric analysis of variance model using a mixed-effects model with repeated statement was fitted to the natural logarithm transferred aGFR obtained at postbaseline visits and baseline.
5.Secondary Outcome
Title Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48
Hide Description CTX is a biomarker of bone turnover.
Time Frame Baseline; Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 226 6
Median (Inter-Quartile Range)
Unit of Measure: percentage change
Change at Week 24 Number Analyzed 226 participants 6 participants
-3.9
(-15.8 to 10.7)
16.9
(0.0 to 21.7)
Change at Week 48 Number Analyzed 222 participants 6 participants
-2.2
(-16.7 to 24.4)
0.0
(-4.8 to 10.8)
6.Secondary Outcome
Title Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48
Hide Description P1NP is a biomarker of bone turnover.
Time Frame Baseline; Weeks 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 229 6
Median (Inter-Quartile Range)
Unit of Measure: percentage change
Change at Week 24 Number Analyzed 229 participants 6 participants
-12.98
(-34.48 to 8.86)
6.44
(-5.08 to 47.62)
Change at Week 48 Number Analyzed 224 participants 6 participants
-25.29
(-45.98 to 2.00)
2.27
(-29.12 to 41.80)
7.Secondary Outcome
Title Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
Hide Description Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.
Time Frame Baseline; Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 227 6
Median (Inter-Quartile Range)
Unit of Measure: percentage change
Change at Week 24 Number Analyzed 227 participants 6 participants
-56.2
(-90.0 to -11.8)
68.8
(-37.1 to 72.6)
Change at Week 48 Number Analyzed 220 participants 6 participants
-68.9
(-92.2 to -20.5)
47.8
(13.3 to 78.9)
Change at Week 96 Number Analyzed 212 participants 6 participants
-64.1
(-91.4 to 9.8)
55.0
(-10.5 to 197.0)
Change at Week 144 Number Analyzed 187 participants 6 participants
-63.8
(-92.4 to 4.6)
-1.0
(-10.2 to 43.4)
8.Secondary Outcome
Title Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
Hide Description Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury.
Time Frame Baseline; Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 224 6
Median (Inter-Quartile Range)
Unit of Measure: percentage change
Change at Week 24 Number Analyzed 224 participants 6 participants
-70.7
(-92.6 to -11.1)
-19.5
(-93.0 to 81.3)
Change at Week 48 Number Analyzed 214 participants 6 participants
-76.5
(-94.6 to -17.7)
-59.2
(-85.0 to 34.3)
Change at Week 96 Number Analyzed 210 participants 6 participants
-83.6
(-96.4 to -31.1)
-45.9
(-95.8 to 195.6)
Change at Week 144 Number Analyzed 185 participants 6 participants
-81.9
(-95.5 to -18.0)
-3.6
(-66.7 to 73.5)
9.Secondary Outcome
Title Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities
Hide Description Adverse events (AEs) and graded laboratory abnormalities occurring during the E/C/F/TAF treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time Frame Baseline up to Week 240 plus 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Measure Type: Number
Unit of Measure: percentage of participants
Any AE 95.5 100.0
Grade 3 or 4 AE 22.3 16.7
AE leading to drug discontinuation 5.0 0
Serious AE 22.7 16.7
Grade 3 or 4 laboratory abnormality 42.6 66.7
10.Secondary Outcome
Title Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144
Hide Description The percentage of participants achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame Weeks 24, 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 95.0 83.3
Week 48 93.0 100.0
Week 96 88.4 100.0
Week 144 81.4 100.0
11.Secondary Outcome
Title Pharmacokinetic (PK) Parameter: Cmax of TAF
Hide Description Cmax is defined as the maximum concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set (enrolled in the PK/PD substudy, received at least 1 dose of study drug, and for whom steady-state PK parameters were available) with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: ng/mL
269.8  (180.77)
12.Secondary Outcome
Title PK Parameter: Tmax of TAF
Hide Description Tmax is defined as the time of Cmax. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Median (Inter-Quartile Range)
Unit of Measure: hours
0.97
(0.50 to 1.98)
13.Secondary Outcome
Title PK Parameter: Clast of TAF
Hide Description Clast is defined as the last observable concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: ng/mL
7.6  (25.73)
14.Secondary Outcome
Title PK Parameter: Tlast of TAF
Hide Description Tlast is defined as the time of Clast. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Median (Inter-Quartile Range)
Unit of Measure: hours
4.45
(3.82 to 5.00)
15.Secondary Outcome
Title PK Parameter: λz of TAF
Hide Description λz is defined as the terminal elimination rate constant. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: 1/hour
1.764  (1.4521)
16.Secondary Outcome
Title PK Parameter: AUCtau of TAF
Hide Description AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
368.4  (631.20)
17.Secondary Outcome
Title PK Parameter: t1/2 of TAF
Hide Description t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the PK Substudy Analysis Set with available data were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 30
Median (Inter-Quartile Range)
Unit of Measure: hours
0.43
(0.37 to 0.52)
18.Secondary Outcome
Title PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study
Hide Description TFV-DP is an active phosphorylated metabolite of tenofovir alafenamide. AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Time Frame Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who were enrolled in the PK/PD substudy, received at least 1 dose of study drug, and for whom the steady-state PK parameter (AUCtau) of TFV-DP was evaluable were analyzed.
Arm/Group Title Substudy Participants
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: µmol*h/L
50.6  (55.75)
19.Secondary Outcome
Title Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144
Hide Description eGFR is a measurement of the kidney's ability to filter blood.
Time Frame Baseline; Weeks 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Baseline Number Analyzed 242 participants 6 participants
55.6
(45.7 to 62.4)
60.2
(45.0 to 63.2)
Change at Week 48 Number Analyzed 225 participants 5 participants
-0.6
(-5.4 to 5.4)
-0.6
(-1.9 to 4.2)
Change at Week 96 Number Analyzed 217 participants 6 participants
0.6
(-4.6 to 7.2)
-1.9
(-4.0 to 6.0)
Change at Week 144 Number Analyzed 206 participants 6 participants
1.5
(-4.8 to 7.2)
7.0
(3.3 to 11.2)
20.Secondary Outcome
Title Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144
Hide Description eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Time Frame Baseline; Weeks 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline Number Analyzed 241 participants 6 participants
69.7
(55.9 to 82.7)
70.2
(64.0 to 100.8)
Change at Week 48 Number Analyzed 224 participants 5 participants
1.7
(-7.3 to 12.0)
7.3
(-0.1 to 12.2)
Change at Week 96 Number Analyzed 216 participants 6 participants
3.2
(-3.6 to 11.8)
5.6
(-7.2 to 20.8)
Change at Week 144 Number Analyzed 205 participants 6 participants
3.1
(-4.8 to 11.8)
3.5
(-1.8 to 22.9)
21.Secondary Outcome
Title Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144
Hide Description eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.
Time Frame Baseline; Weeks 48, 96, and 144
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set with available data at the respective time point were analyzed.
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description:
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
Overall Number of Participants Analyzed 242 6
Median (Inter-Quartile Range)
Unit of Measure: mL/min/1.73 m^2
Baseline Number Analyzed 242 participants 6 participants
54.1
(46.0 to 62.8)
54.4
(41.7 to 81.4)
Change at Week 48 Number Analyzed 226 participants 5 participants
-1.7
(-7.9 to 4.2)
-3.0
(-4.9 to 0.6)
Change at Week 96 Number Analyzed 217 participants 6 participants
0.1
(-5.7 to 6.4)
-3.1
(-9.5 to 2.1)
Change at Week 144 Number Analyzed 206 participants 6 participants
1.7
(-5.3 to 8.5)
0.9
(-5.7 to 6.0)
Time Frame First dose date up to Week 240 plus 30 days
Adverse Event Reporting Description Safety Analysis Set included participants were enrolled and received at least 1 dose of study drug.
 
Arm/Group Title Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Hide Arm/Group Description E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 240 weeks in ART-experienced participants E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food for up to 188 weeks in ART-naive participants
All-Cause Mortality
Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Affected / at Risk (%) Affected / at Risk (%)
Total   55/242 (22.73%)   1/6 (16.67%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  1/242 (0.41%)  0/6 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  1/242 (0.41%)  0/6 (0.00%) 
Acute myocardial infarction  1  4/242 (1.65%)  0/6 (0.00%) 
Cardiac arrest  1  1/242 (0.41%)  0/6 (0.00%) 
Cardiac failure congestive  1  2/242 (0.83%)  0/6 (0.00%) 
Cardio-respiratory arrest  1  1/242 (0.41%)  0/6 (0.00%) 
Myocardial infarction  1  1/242 (0.41%)  0/6 (0.00%) 
Palpitations  1  1/242 (0.41%)  0/6 (0.00%) 
Supraventricular extrasystoles  1  1/242 (0.41%)  0/6 (0.00%) 
Eye disorders     
Blindness unilateral  1  1/242 (0.41%)  0/6 (0.00%) 
Vitreous detachment  1  1/242 (0.41%)  0/6 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/242 (0.83%)  0/6 (0.00%) 
Abdominal pain upper  1  1/242 (0.41%)  0/6 (0.00%) 
Colitis  1  1/242 (0.41%)  0/6 (0.00%) 
Dysphagia  1  1/242 (0.41%)  0/6 (0.00%) 
Large intestinal obstruction  1  1/242 (0.41%)  0/6 (0.00%) 
Pancreatitis acute  1  1/242 (0.41%)  0/6 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  1/242 (0.41%)  0/6 (0.00%) 
Cholecystitis  1  1/242 (0.41%)  0/6 (0.00%) 
Infections and infestations     
Abscess neck  1  1/242 (0.41%)  0/6 (0.00%) 
Acute hepatitis c  1  1/242 (0.41%)  0/6 (0.00%) 
Appendicitis  1  1/242 (0.41%)  0/6 (0.00%) 
Bronchitis  1  2/242 (0.83%)  0/6 (0.00%) 
Clostridium difficile colitis  1  1/242 (0.41%)  0/6 (0.00%) 
Device related infection  1  1/242 (0.41%)  0/6 (0.00%) 
Endophthalmitis  1  1/242 (0.41%)  0/6 (0.00%) 
Gastroenteritis  1  2/242 (0.83%)  0/6 (0.00%) 
Gastrointestinal viral infection  1  1/242 (0.41%)  0/6 (0.00%) 
Influenza  1  1/242 (0.41%)  0/6 (0.00%) 
Localised infection  1  1/242 (0.41%)  0/6 (0.00%) 
Ophthalmic herpes zoster  1  1/242 (0.41%)  0/6 (0.00%) 
Pneumonia  1  4/242 (1.65%)  0/6 (0.00%) 
Pneumonia bacterial  1  1/242 (0.41%)  0/6 (0.00%) 
Pneumonia staphylococcal  1  1/242 (0.41%)  0/6 (0.00%) 
Pyelonephritis acute  1  1/242 (0.41%)  0/6 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/242 (0.41%)  0/6 (0.00%) 
Fall  1  1/242 (0.41%)  0/6 (0.00%) 
Rib fracture  1  1/242 (0.41%)  0/6 (0.00%) 
Spinal compression fracture  1  1/242 (0.41%)  0/6 (0.00%) 
Sternal fracture  1  1/242 (0.41%)  0/6 (0.00%) 
Investigations     
Weight decreased  1  1/242 (0.41%)  0/6 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  3/242 (1.24%)  0/6 (0.00%) 
Hyperglycaemia  1  1/242 (0.41%)  0/6 (0.00%) 
Hypoglycaemia  1  1/242 (0.41%)  0/6 (0.00%) 
Hypovolaemia  1  1/242 (0.41%)  0/6 (0.00%) 
Type 2 diabetes mellitus  1  2/242 (0.83%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/242 (0.83%)  0/6 (0.00%) 
Osteonecrosis  1  1/242 (0.41%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder transitional cell carcinoma  1  1/242 (0.41%)  0/6 (0.00%) 
Invasive ductal breast carcinoma  1  1/242 (0.41%)  0/6 (0.00%) 
Lung neoplasm malignant  1  1/242 (0.41%)  0/6 (0.00%) 
Malignant neoplasm of unknown primary site  1  1/242 (0.41%)  0/6 (0.00%) 
Renal cell carcinoma  1  1/242 (0.41%)  0/6 (0.00%) 
Transitional cell carcinoma  1  1/242 (0.41%)  0/6 (0.00%) 
Nervous system disorders     
Cervical radiculopathy  1  1/242 (0.41%)  0/6 (0.00%) 
Facial paralysis  1  1/242 (0.41%)  0/6 (0.00%) 
Loss of consciousness  1  1/242 (0.41%)  0/6 (0.00%) 
Syncope  1  2/242 (0.83%)  0/6 (0.00%) 
Transient ischaemic attack  1  1/242 (0.41%)  0/6 (0.00%) 
Psychiatric disorders     
Drug dependence  1  1/242 (0.41%)  0/6 (0.00%) 
Major depression  1  1/242 (0.41%)  0/6 (0.00%) 
Suicidal ideation  1  0/242 (0.00%)  1/6 (16.67%) 
Suicide attempt  1  1/242 (0.41%)  0/6 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  2/242 (0.83%)  0/6 (0.00%) 
Chronic kidney disease  1  1/242 (0.41%)  0/6 (0.00%) 
Urinary retention  1  1/242 (0.41%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  2/242 (0.83%)  0/6 (0.00%) 
Pulmonary embolism  1  1/242 (0.41%)  0/6 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/242 (0.41%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 21.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1 (Treatment-experienced) Cohort 2 (Treatment-naive)
Affected / at Risk (%) Affected / at Risk (%)
Total   195/242 (80.58%)   5/6 (83.33%) 
Cardiac disorders     
Supraventricular extrasystoles  1  1/242 (0.41%)  1/6 (16.67%) 
Gastrointestinal disorders     
Constipation  1  16/242 (6.61%)  0/6 (0.00%) 
Diarrhoea  1  32/242 (13.22%)  1/6 (16.67%) 
Gingival pain  1  0/242 (0.00%)  1/6 (16.67%) 
Mouth ulceration  1  2/242 (0.83%)  1/6 (16.67%) 
Nausea  1  22/242 (9.09%)  0/6 (0.00%) 
Vomiting  1  13/242 (5.37%)  0/6 (0.00%) 
General disorders     
Chest pain  1  10/242 (4.13%)  1/6 (16.67%) 
Fatigue  1  20/242 (8.26%)  1/6 (16.67%) 
Peripheral swelling  1  8/242 (3.31%)  1/6 (16.67%) 
Infections and infestations     
Bronchitis  1  37/242 (15.29%)  1/6 (16.67%) 
Hordeolum  1  1/242 (0.41%)  1/6 (16.67%) 
Influenza  1  10/242 (4.13%)  1/6 (16.67%) 
Nasopharyngitis  1  25/242 (10.33%)  0/6 (0.00%) 
Sinusitis  1  18/242 (7.44%)  0/6 (0.00%) 
Upper respiratory tract infection  1  39/242 (16.12%)  1/6 (16.67%) 
Urinary tract infection  1  25/242 (10.33%)  0/6 (0.00%) 
Injury, poisoning and procedural complications     
Exposure to communicable disease  1  1/242 (0.41%)  1/6 (16.67%) 
Investigations     
Cardiac murmur  1  1/242 (0.41%)  1/6 (16.67%) 
Electrocardiogram st-t change  1  0/242 (0.00%)  1/6 (16.67%) 
Metabolism and nutrition disorders     
Dyslipidaemia  1  5/242 (2.07%)  1/6 (16.67%) 
Hyperlipidaemia  1  7/242 (2.89%)  2/6 (33.33%) 
Hypokalaemia  1  3/242 (1.24%)  1/6 (16.67%) 
Vitamin d deficiency  1  4/242 (1.65%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  34/242 (14.05%)  1/6 (16.67%) 
Arthritis  1  3/242 (1.24%)  1/6 (16.67%) 
Back pain  1  27/242 (11.16%)  0/6 (0.00%) 
Osteopenia  1  26/242 (10.74%)  0/6 (0.00%) 
Osteoporosis  1  13/242 (5.37%)  1/6 (16.67%) 
Pain in extremity  1  25/242 (10.33%)  2/6 (33.33%) 
Tendonitis  1  5/242 (2.07%)  1/6 (16.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts  1  1/242 (0.41%)  1/6 (16.67%) 
Nervous system disorders     
Dizziness  1  18/242 (7.44%)  0/6 (0.00%) 
Headache  1  20/242 (8.26%)  1/6 (16.67%) 
Migraine  1  2/242 (0.83%)  1/6 (16.67%) 
Paraesthesia  1  13/242 (5.37%)  0/6 (0.00%) 
Somnolence  1  3/242 (1.24%)  1/6 (16.67%) 
Renal and urinary disorders     
Proteinuria  1  3/242 (1.24%)  1/6 (16.67%) 
Renal cyst  1  14/242 (5.79%)  0/6 (0.00%) 
Reproductive system and breast disorders     
Erectile dysfunction  1  6/242 (2.48%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  24/242 (9.92%)  1/6 (16.67%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  4/242 (1.65%)  1/6 (16.67%) 
Pruritus  1  4/242 (1.65%)  1/6 (16.67%) 
Rash  1  15/242 (6.20%)  0/6 (0.00%) 
Rash generalised  1  1/242 (0.41%)  1/6 (16.67%) 
Vascular disorders     
Hypertension  1  24/242 (9.92%)  0/6 (0.00%) 
Orthostatic hypotension  1  1/242 (0.41%)  1/6 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 21.0
Enrollment in Cohort 2 (treatment-naive) was low, which affects the interpretation of the data.
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01818596    
Other Study ID Numbers: GS-US-292-0112
2013-000516-25 ( EudraCT Number )
First Submitted: March 22, 2013
First Posted: March 26, 2013
Results First Submitted: December 4, 2015
Results First Posted: February 18, 2016
Last Update Posted: March 2, 2020