The primary objective of this study is to evaluate the effect of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) tablet on renal parameters at Week 24 in treatment-naive and treatment-experienced HIV-positive, adults with mild to moderate renal impairment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
252
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
eGFR is a measurement of the kidney's ability to filter blood.
Time frame: Baseline; Week 24
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
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
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
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
Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy
aGFR was directly measured using iohexol plasma clearance (CLiohexol).
Time frame: Baseline; Week 2, 4, or 8; Week 24
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48
CTX is a biomarker of bone turnover.
Time frame: Baseline; Weeks 24 and 48
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48
P1NP is a biomarker of bone turnover.
Time frame: Baseline; Weeks 24 and 48
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
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Maricopa Integrated Health System - McDowell Clinic
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Los Angeles, California, United States
Peter J Ruane, MD, Inc
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Anthony Mills MD, Inc
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Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group
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...and 60 more locations
Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.
Time frame: Baseline; Weeks 24, 48, 96, and 144
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
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
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities
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
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144
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
Pharmacokinetic (PK) Parameter: Cmax of TAF
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
PK Parameter: Tmax of TAF
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
PK Parameter: Clast of TAF
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
PK Parameter: Tlast of TAF
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
PK Parameter: λz of TAF
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
PK Parameter: AUCtau of TAF
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
PK Parameter: t1/2 of TAF
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
PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study
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
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144
eGFR is a measurement of the kidney's ability to filter blood.
Time frame: Baseline; Weeks 48, 96, and 144
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144
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
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144
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