HIV-1 Infection
Conditions
Keywords
End stage renal disease, Hemodialysis, Open-label, HIV-1 Infection
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV-1) infected adults with end-stage renal disease (ESRD) on chronic hemodialysis (HD).
Interventions
DRUGE/C/F/TAF
150/150/200/10 mg FDC tablets administered orally once daily
DRUGB/F/TAF
50/200/25 mg FDC tablets administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Currently on a stable antiretroviral regimen for ≥ 6 consecutive months * Plasma HIV-1 ribonucleic acid (RNA) concentrations \< 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA \< 50 copies/mL at screening * No documented history of HIV-1 resistance to elvitegravir (EVG), emtricitabine (FTC), lamivudine (3TC) or tenofovir (TFV) and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance * Cluster determinant 4 (CD4+) T cell count ≥ 200 cells/μL * ESRD with estimated glomerular filtration rate (eGFR) \< 15 mL/min by Cockcroft-Gault formula for creatinine clearance * On chronic HD for ≥ 6 months prior to screening * Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL) Key
Exclusion criteria
* Hepatitis B co-infection * Any clinical history, condition, or test result that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements * Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial. * History or presence of allergy or intolerance to the study drugs or their components * A new acquired immunodeficiency syndrome (AIDS)-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis * Received solid organ or bone marrow transplant Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48 | First Dose Date Up to Week 48 | Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug or all AEs for participants still on E/C/F/TAF. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | Week 24 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant'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. |
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm | Week 48 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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. |
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm | Week 96 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant'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. |
| Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | AUCtau is defined as area under the concentration versus time curve over the dosing interval (i.e., concentration of drug over time). |
| PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | AUClast is defined as the area under the concentration versus time curve from time zero to the last observable concentration. |
| PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | Cmax is defined as the maximum concentration of drug. |
| PK Parameter: Ctau of EVG, COBI, FTC, and TFV | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | Ctau is defined as the observed drug concentration at the end of the dosing interval. Ctau has been presented in lieu of Cmin (specified in the protocol) to align with other Gilead studies. This change has no impact on the PK analysis as Ctau and Cmin are equivalent for all analytes. |
| GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96 | First Dose Date Up to Week 96 | Treatment-emergent Adverse Events (TEAE) were defined as events that met 1 or both of the following criteria as any AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug for participants who did not participate in the BVY OL extension phase or the day prior to the date of the first B/F/TAF study drug dose for participants who participated in the BVY OL extension phase. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). |
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach | Week 96 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions. |
| BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach | Week 48 of the BVY OL Extension Phase | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions. |
| GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96 | Baseline; Week 96 | — |
| BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 of the BVY OL Extension Phase | — |
| GEN Phase: Change From Baseline in CD4 Percentage at Week 96 | Baseline; Week 96 | — |
| BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 | Baseline; Week 48 of the BVY OL Extension Phase | — |
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach | Week 96 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 were analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL. |
Countries
Austria, France, Germany, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe and the United States. The first participant was screened on 14 December 2015. The last study visit occurred on 15 October 2019.
Pre-assignment details
75 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| E/C/F/TAF (GEN Phase) Participants received elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (Genvoya®, GEN) (150/150/200/10 mg) fixed-dose combination (FDC) tablet once daily with food for 96 weeks. At Week 96, participants in the United States (US) who wished to participate in the open-label (OL) rollover extension either discontinued E/C/F/TAF FDC or continued to take E/C/F/TAF FDC for up to 114 weeks. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| GEN Phase | Adverse Event | 2 | 0 |
| GEN Phase | Death | 2 | 0 |
| GEN Phase | Investigator's Discretion | 4 | 0 |
| GEN Phase | Lost to Follow-up | 2 | 0 |
| GEN Phase | Non-Compliance with Study Drug | 1 | 0 |
| GEN Phase | Withdrew Consent | 5 | 0 |
Baseline characteristics
| Characteristic | E/C/F/TAF (GEN Phase) |
|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 11 |
| CD4+ Cell Count Categories >= 200 to < 350 cells/µL | 12 Participants |
| CD4+ Cell Count Categories >= 350 to < 500 cells/µL | 14 Participants |
| CD4+ Cell Count Categories >= 500 cells/µL | 29 Participants |
| CD4+ Cell Count Categories < 50 cells/µL | 0 Participants |
| CD4+ Cell Count Categories >= 50 to < 200 cells/µL | 0 Participants |
| CD4 Percentage | 31.5 percentage of CD4 cells STANDARD_DEVIATION 9.41 |
| Cluster Determinant 4+ (CD4+) Cell Count | 545 cells/µL STANDARD_DEVIATION 239.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HIV-1 RNA Category < 50 copies/mL | 54 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment Austria | 1 Participants |
| Region of Enrollment France | 7 Participants |
| Region of Enrollment Germany | 1 Participants |
| Region of Enrollment United States | 46 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 55 | 0 / 10 |
| other Total, other adverse events | 41 / 55 | 10 / 10 |
| serious Total, serious adverse events | 36 / 55 | 3 / 10 |
Outcome results
Primary
GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48
Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug or all AEs for participants still on E/C/F/TAF. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening).
Time frame: First Dose Date Up to Week 48
Population: The GEN Safety Analysis Set included participants who were enrolled and received at least 1 dose of GEN (E/C/F/TAF FDC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48 | 32.7 percentage of participants |
Secondary
BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline; Week 48 of the BVY OL Extension Phase
Population: Participants in the BVY Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF (GEN Phase) | BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48 | Baseline | 581 cells/µL | Standard Deviation 146.8 |
| E/C/F/TAF (GEN Phase) | BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48 | Change from Baseline at Week 48 | -104 cells/µL | Standard Deviation 120.8 |
Secondary
BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48
Time frame: Baseline; Week 48 of the BVY OL Extension Phase
Population: Participants in the BVY Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF (GEN Phase) | BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 | Baseline | 31.9 percentage of CD4 cells | Standard Deviation 7.37 |
| E/C/F/TAF (GEN Phase) | BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 | Change from Baseline at Week 48 | 1.7 percentage of CD4 cells | Standard Deviation 4.39 |
Secondary
BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
Time frame: Week 48 of the BVY OL Extension Phase
Population: The BVY Full Analysis Set included all participants who were enrolled in the study and received at least 1 dose of BVY (B/F/TAF FDC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach | 100.0 percentage of participants |
Secondary
GEN Phase: Change From Baseline in CD4 Percentage at Week 96
Time frame: Baseline; Week 96
Population: Participants in the GEN Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Change From Baseline in CD4 Percentage at Week 96 | 2.8 percentage of CD4 cells | Standard Deviation 6.37 |
Secondary
GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96
Time frame: Baseline; Week 96
Population: Participants in the GEN Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96 | -35 cells/µL | Standard Deviation 218.3 |
Secondary
GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96
Treatment-emergent Adverse Events (TEAE) were defined as events that met 1 or both of the following criteria as any AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug for participants who did not participate in the BVY OL extension phase or the day prior to the date of the first B/F/TAF study drug dose for participants who participated in the BVY OL extension phase. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening).
Time frame: First Dose Date Up to Week 96
Population: Participants in the GEN Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96 | 43.6 percentage of participants |
Secondary
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant'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: Week 24
Population: The GEN Full Analysis Set included participants who were enrolled and received at least 1 dose of GEN (E/C/F/TAF FDC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | 87.3 percentage of participants |
Secondary
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant'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: Week 48
Population: Participants in the GEN Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm | 81.8 percentage of participants |
Secondary
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant'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: Week 96
Population: Participants in the GEN Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm | 54.5 percentage of participants |
Secondary
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.
Time frame: Week 96
Population: Participants in the GEN Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach | 100.0 percentage of participants |
Secondary
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 were analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.
Time frame: Week 96
Population: Participants in the GEN Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF (GEN Phase) | GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach | 61.8 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV)
AUCtau is defined as area under the concentration versus time curve over the dosing interval (i.e., concentration of drug over time).
Time frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Population: Participants in the PK Substudy Analysis Set (participants who were enrolled into the study, participated in the intensive PK substudy, received at least 1 dose of E/C/F/TAF FDC, and had at least 1 nonmissing plasma PK concentration value for any analyte of interest) with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF (GEN Phase) | Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) | EVG | 14284.8 h*ng/mL | Standard Deviation 7790.26 |
| E/C/F/TAF (GEN Phase) | Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) | COBI | 10179.5 h*ng/mL | Standard Deviation 6009.28 |
| E/C/F/TAF (GEN Phase) | Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) | FTC | 62929.9 h*ng/mL | Standard Deviation 30199.63 |
| E/C/F/TAF (GEN Phase) | Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) | TFV | 8715.0 h*ng/mL | Standard Deviation 3432.16 |
Secondary
PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV
AUClast is defined as the area under the concentration versus time curve from time zero to the last observable concentration.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF (GEN Phase) | PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | EVG | 12857.6 h*ng/mL | Standard Deviation 7894.09 |
| E/C/F/TAF (GEN Phase) | PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | COBI | 9558.7 h*ng/mL | Standard Deviation 5963.16 |
| E/C/F/TAF (GEN Phase) | PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | FTC | 59057.4 h*ng/mL | Standard Deviation 31485.96 |
| E/C/F/TAF (GEN Phase) | PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | TAF | 231.9 h*ng/mL | Standard Deviation 123.46 |
| E/C/F/TAF (GEN Phase) | PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | TFV | 7664.2 h*ng/mL | Standard Deviation 3958.36 |
Secondary
PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV
Cmax is defined as the maximum concentration of drug.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF (GEN Phase) | PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | EVG | 1258.5 ng/mL | Standard Deviation 689.57 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | COBI | 1370.4 ng/mL | Standard Deviation 920.15 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | FTC | 4875.0 ng/mL | Standard Deviation 1981.03 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | TAF | 246.3 ng/mL | Standard Deviation 185.69 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | TFV | 442.8 ng/mL | Standard Deviation 181.03 |
Secondary
PK Parameter: Ctau of EVG, COBI, FTC, and TFV
Ctau is defined as the observed drug concentration at the end of the dosing interval. Ctau has been presented in lieu of Cmin (specified in the protocol) to align with other Gilead studies. This change has no impact on the PK analysis as Ctau and Cmin are equivalent for all analytes.
Time frame: 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4
Population: Participants in the PK Substudy Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF (GEN Phase) | PK Parameter: Ctau of EVG, COBI, FTC, and TFV | EVG | 174.4 ng/mL | Standard Deviation 104.36 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Ctau of EVG, COBI, FTC, and TFV | COBI | 28.9 ng/mL | Standard Deviation 34.06 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Ctau of EVG, COBI, FTC, and TFV | FTC | 1277.3 ng/mL | Standard Deviation 756.6 |
| E/C/F/TAF (GEN Phase) | PK Parameter: Ctau of EVG, COBI, FTC, and TFV | TFV | 264.8 ng/mL | Standard Deviation 193.98 |